Pub Date : 2021-05-03DOI: 10.15789/1563-0625-MTM-2141
A. Korenevsky, Yuliya P. Milyutina, M. E. Berezkina, E. P. Alexandrova, O. Balabas, K. Markova, S. Selkov, D. Sokolov
Extracellular vesicles that are shed from the plasma membranes take an active part in intercellular communication, transporting a wide range of molecules, including proteins, lipids, nucleic acids and carbohydrates, being of great functional importance. One of the steps to better understanding of distant communications of cells and their regulatory mechanisms is a proteomic study of various extracellular vesicles, including microvesicles and exosomes. Pro-inflammatory cytokines produced by monocytes and individual complement system components play a key role in their specific functioning. The aim of this work was to study proteomic composition of THP-1 monocyte-like cells and their microvesicles. The MALDI-mass spectrometric analysis of electrophoretic protein fractions of cell lysates and microvesicles allowed for identifying 107 proteins that perform various functions. Among 19 determined functional groups, the largest ones comprise transcription regulators and proteins with unknown functions. The smallest functional groups include regulators of cell differentiation and development, proteins participating in immune response and inflammation, cellular receptors and their regulators, transporter and transport regulatory proteins, as well as cell proteins mediating adhesion and matrix structures, processing regulators, proteins of ubiquitin-proteasome system, intracellular signaling, autophagy and exocytosis regulators, chromatin structural proteins, hemostatic regulators, and peptide hormones. An intermediate position is occupied by cytokines and growth factors, enzymes, cytoskeleton and motor proteins, as well as RNA processing and translation regulators. The subsequent DAVID Functional Annotation Clustering analysis allowed for identifying the most common groups distributed by their molecular function, biological processes, and cellular component. Separately, in the microvesicles derived from THP-1 monocyte-like cells, proteins of the immune response and inflammation, cytokines and growth factors, intracellular signaling proteins, cell differentiation regulators and developmental proteins, as well as cell adhesion and matrix proteins were identified among other protein molecules. The data obtained on the partial proteome of THP-1 monocyte-like cells and their microvesicles extend the existing knowledge on distant communications between the cells and suggest new mechanisms of interaction between monocytes/macrophages and their microenvironment.
{"title":"MALDI-TOF mass spectrometric protein profiling of THP-1 cells and their microvesicles","authors":"A. Korenevsky, Yuliya P. Milyutina, M. E. Berezkina, E. P. Alexandrova, O. Balabas, K. Markova, S. Selkov, D. Sokolov","doi":"10.15789/1563-0625-MTM-2141","DOIUrl":"https://doi.org/10.15789/1563-0625-MTM-2141","url":null,"abstract":"Extracellular vesicles that are shed from the plasma membranes take an active part in intercellular communication, transporting a wide range of molecules, including proteins, lipids, nucleic acids and carbohydrates, being of great functional importance. One of the steps to better understanding of distant communications of cells and their regulatory mechanisms is a proteomic study of various extracellular vesicles, including microvesicles and exosomes. Pro-inflammatory cytokines produced by monocytes and individual complement system components play a key role in their specific functioning. The aim of this work was to study proteomic composition of THP-1 monocyte-like cells and their microvesicles. The MALDI-mass spectrometric analysis of electrophoretic protein fractions of cell lysates and microvesicles allowed for identifying 107 proteins that perform various functions. Among 19 determined functional groups, the largest ones comprise transcription regulators and proteins with unknown functions. The smallest functional groups include regulators of cell differentiation and development, proteins participating in immune response and inflammation, cellular receptors and their regulators, transporter and transport regulatory proteins, as well as cell proteins mediating adhesion and matrix structures, processing regulators, proteins of ubiquitin-proteasome system, intracellular signaling, autophagy and exocytosis regulators, chromatin structural proteins, hemostatic regulators, and peptide hormones. An intermediate position is occupied by cytokines and growth factors, enzymes, cytoskeleton and motor proteins, as well as RNA processing and translation regulators. The subsequent DAVID Functional Annotation Clustering analysis allowed for identifying the most common groups distributed by their molecular function, biological processes, and cellular component. Separately, in the microvesicles derived from THP-1 monocyte-like cells, proteins of the immune response and inflammation, cytokines and growth factors, intracellular signaling proteins, cell differentiation regulators and developmental proteins, as well as cell adhesion and matrix proteins were identified among other protein molecules. The data obtained on the partial proteome of THP-1 monocyte-like cells and their microvesicles extend the existing knowledge on distant communications between the cells and suggest new mechanisms of interaction between monocytes/macrophages and their microenvironment. ","PeriodicalId":85139,"journal":{"name":"Medical immunology (London, England)","volume":"23 1","pages":"275-292"},"PeriodicalIF":0.0,"publicationDate":"2021-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46490313","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-05-03DOI: 10.15789/1563-0625-EAP-2147
V. Beloglazov, I. Yatskov, Rean Hayrievna Useinova
Chronic obstructive pulmonary disease (COPD) is a progressive disease characterized by irreversible or partially reversible obstruction of the bronchial tree. Currently, there are many proven links in the COPD etiopathogenesis, among which a pivotal role is assigned to the value of the hyperergic inflammatory reaction in response to inhalation of various harmful substances (tobacco smoke, industrial pollutants, etc.). The number of macrophages, neutrophils, lymphocytes increases in the lungs of COPD patients, and these cells secrete a fairly wide range of inflammatory mediators. Bacterial colonization of the airways is one of the key features in COPD pathogenesis leading to persistent or chronic stimulation of immune cells through Tolllike receptors (TLR), which perceive the pathogen-associated molecular patterns (PAMPs).This article provides a review of literature concerning modern concepts of the role of Toll-like receptors expression and polymorphism, in particular, TLR4, in pathogenesis of COPD. TLR4 is a member of the Tolllike receptor family that plays a fundamental role in pathogen identification and innate immune activation. By recognizing the pathogen-associated molecular patterns (PAMPs) expressed on infectious agents, TLRs mediate the production of cytokines necessary for the development of effective immunity. Different TLRs exhibit distinct expression patterns. This receptor is most abundantly expressed in placenta and in the myelomonocytic leukocyte subpopulations. E.g., Di Stefano A. et al. (2017), determined immunohistochemically the expression levels of TLR2, TLR4, TLR9, NOD1, NOD2, CD14, Toll-interleukin-1-receptor domain containing adapter protein (TIRAP) and interleukin-1-receptor-associated phosphokinases (IRAK1 and IRAK4) in bronchial mucosa of patients with stable COPD of varying severity. It was found that TLR4 expression of the bronchial epithelium positively correlated with degree of obstruction and CD4+ and CD8+T cell contents. Stimulation of TLR4 increases cytokine production, which may be a relevant mechanism by which bacteria cause excessive inflammation in COPD patients. The degree of TLR4 involvement into COPD pathogenesis requires more detailed study in future, in order to determine the main mechanisms for emerging inflammatory response in the airways. This review article is part of a research grant project to study pro-inflammatory response to endotoxin of Gram-negative flora in COPD pathogenesis (State registration number – АААА-А19-119122390040-2).
{"title":"Expression and polymorphism of lTLR4 receptors in pathogenesis of chronic obstructive pulmonary disease: a modern view","authors":"V. Beloglazov, I. Yatskov, Rean Hayrievna Useinova","doi":"10.15789/1563-0625-EAP-2147","DOIUrl":"https://doi.org/10.15789/1563-0625-EAP-2147","url":null,"abstract":"Chronic obstructive pulmonary disease (COPD) is a progressive disease characterized by irreversible or partially reversible obstruction of the bronchial tree. Currently, there are many proven links in the COPD etiopathogenesis, among which a pivotal role is assigned to the value of the hyperergic inflammatory reaction in response to inhalation of various harmful substances (tobacco smoke, industrial pollutants, etc.). The number of macrophages, neutrophils, lymphocytes increases in the lungs of COPD patients, and these cells secrete a fairly wide range of inflammatory mediators. Bacterial colonization of the airways is one of the key features in COPD pathogenesis leading to persistent or chronic stimulation of immune cells through Tolllike receptors (TLR), which perceive the pathogen-associated molecular patterns (PAMPs).This article provides a review of literature concerning modern concepts of the role of Toll-like receptors expression and polymorphism, in particular, TLR4, in pathogenesis of COPD. TLR4 is a member of the Tolllike receptor family that plays a fundamental role in pathogen identification and innate immune activation. By recognizing the pathogen-associated molecular patterns (PAMPs) expressed on infectious agents, TLRs mediate the production of cytokines necessary for the development of effective immunity. Different TLRs exhibit distinct expression patterns. This receptor is most abundantly expressed in placenta and in the myelomonocytic leukocyte subpopulations. E.g., Di Stefano A. et al. (2017), determined immunohistochemically the expression levels of TLR2, TLR4, TLR9, NOD1, NOD2, CD14, Toll-interleukin-1-receptor domain containing adapter protein (TIRAP) and interleukin-1-receptor-associated phosphokinases (IRAK1 and IRAK4) in bronchial mucosa of patients with stable COPD of varying severity. It was found that TLR4 expression of the bronchial epithelium positively correlated with degree of obstruction and CD4+ and CD8+T cell contents. Stimulation of TLR4 increases cytokine production, which may be a relevant mechanism by which bacteria cause excessive inflammation in COPD patients. The degree of TLR4 involvement into COPD pathogenesis requires more detailed study in future, in order to determine the main mechanisms for emerging inflammatory response in the airways. This review article is part of a research grant project to study pro-inflammatory response to endotoxin of Gram-negative flora in COPD pathogenesis (State registration number – АААА-А19-119122390040-2).","PeriodicalId":85139,"journal":{"name":"Medical immunology (London, England)","volume":"23 1","pages":"231-236"},"PeriodicalIF":0.0,"publicationDate":"2021-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49213948","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-05-03DOI: 10.15789/1563-0625-SOR-2155
L. Gordeeva, E. Voronina, E. Polenok, S. Mun, S. L. Nersesyan, R. V. Olennikova, M. Filipenko, A. Glushkov
The relationship between the HLA-G gene polymorphism (rs41551813, rs12722477, rs41557518), intrauterine infection and recurrent miscarriage (RM) in women were studied. The case group consisted of 180 patients with RM, defined as two or more consecutive miscarriages (min = 2; max = 8) at up to 20 weeks of gestation, and with clinically confirmed pregnancies and non-viable fetuses. At the time of examination. the women were enrolled from the Genetic Counseling Center at the Kemerovo Regional Clinical Hospital, Kemerovo, Russia, and were not pregnant. Each patient underwent a gynecological examination. We excluded women with a history of medical abortion, birth, and ectopic pregnancies. In addition, we excluded women with endocrine (e.g. diabetes) disorders. To exclude other known causes of spontaneous abortion, the following tests were performed: ultrasound examination of pelvic organs, and karyotyping in women and men. The women’s mean age in the RM group, was 29.6±4.8 (SD) years. The control group comprised 408 fertile women. These women didn’t have a history of spontaneous abortion, or a family history of congenital malformations. They have born, at least, 1-2 healthy children. Women’s mean age at birth of last child was 26.8±5.2 (SD) years. Influence of the intrauterine infection was analyzed on the basis of laboratory tests. Diagnostics of bacterial vaginosis and vulvo-vaginal candidiasis by microscopic examination was conducted. Viral agent infections (herpes simplex virus type 2, cytomegalovirus, human papilloma virus type 16/18), Chlamydia trachomatis, Mycoplasma hominis, Ureaplasma urealyticum, Gardnerella vaginalis and Trichomonas vaginalis were detected by enzyme-linked immunoassay and polymerase chain reaction (PCR). The data were obtained from the medical cards of the surveyed women. All the women gave a written informed consent before participating in the study. Typing of polymorphisms of Thr31Ser (rs41551813, HLA-G*01:03) in exon 2, Leu110Ile (rs12722477, HLA-G*01:04) and 1597 delС (rs41557518, HLA-G*01:05N) in exon 3 HLA-G genes were performed by realtime PCR followed by melting analysis. The study showed that the intrauterine infection was not a risk factor for RM (p = 0.30) in the examined women. It was found that the 110 Ile allele (HLA-G *01:04) was a risk factor for RM both in women with intrauterine infection [ORa = 4.50 (2.41-8.38), p = 2.09e-06], and in women without infection [ORa = 2.46 (1.44-4.21), p = 0.0009]. The cooperative influence of genetic and infections factors with the risk of RM in women was revealed [ORa+f = 3.50 (2.01-6.09), p = 8.78e-06]. Our results will be useful in understanding the molecular mechanisms of immune disorders in fetomaternal interface, and for choosing the strategy of management and treatment in women with RM.
研究女性HLA-G基因多态性(rs41551813、rs12722477、rs41557518)与宫内感染及复发性流产(RM)的关系。病例组由180例RM患者组成，定义为连续两次或两次以上流产(min = 2;Max = 8)，妊娠20周以内，临床证实妊娠且胎儿不能存活。在考试的时候。这些妇女来自俄罗斯克麦罗沃地区临床医院的遗传咨询中心，没有怀孕。每位患者都进行了妇科检查。我们排除了有药物流产、分娩和异位妊娠史的妇女。此外，我们排除了患有内分泌(如糖尿病)疾病的女性。为了排除其他已知的自然流产原因，进行了以下检查:盆腔器官超声检查和男女核型分析。RM组女性的平均年龄为29.6±4.8 (SD)岁。对照组由408名育龄妇女组成。这些妇女没有自然流产史，也没有先天性畸形的家族史。他们至少生了1-2个健康的孩子。产妇最后一胎平均年龄为26.8±5.2 (SD)岁。在实验室检查的基础上，分析了宫内感染的影响。对细菌性阴道病和外阴阴道念珠菌病进行镜检诊断。采用酶联免疫法和聚合酶链反应(PCR)检测单纯疱疹病毒2型、巨细胞病毒、人乳头瘤病毒16/18型、沙眼衣原体、人支原体、解脲原体、阴道加德纳菌和阴道毛滴虫等病毒感染。数据来自被调查妇女的医疗卡。所有女性在参与研究前都有书面的知情同意书。采用实时聚合酶链反应(real - time PCR)和熔解分析方法，对2外显子Thr31Ser (rs41551813, HLA-G*01:03)、3外显子Leu110Ile (rs12722477, HLA-G*01:04)和1597 delС (rs41557518, HLA-G*01:05N)基因多态性进行分型。研究表明，宫内感染不是RM的危险因素(p = 0.30)。发现110 Ile等位基因(HLA-G *01:04)是宫内感染妇女(ORa = 4.50 (2.41-8.38)， p = 2.09e-06)和未感染妇女(ORa = 2.46 (1.44-4.21)， p = 0.0009)发生RM的危险因素。遗传和感染因素对女性RM风险的共同影响[ORa+f = 3.50 (2.01-6.09)， p = 8.78e-06]。我们的研究结果将有助于了解母婴界面免疫紊乱的分子机制，以及选择RM妇女的管理和治疗策略。
{"title":"Study of relationships between HLA-G gene polymorphism, intrauterine infection and recurrent miscarriage in women","authors":"L. Gordeeva, E. Voronina, E. Polenok, S. Mun, S. L. Nersesyan, R. V. Olennikova, M. Filipenko, A. Glushkov","doi":"10.15789/1563-0625-SOR-2155","DOIUrl":"https://doi.org/10.15789/1563-0625-SOR-2155","url":null,"abstract":"The relationship between the HLA-G gene polymorphism (rs41551813, rs12722477, rs41557518), intrauterine infection and recurrent miscarriage (RM) in women were studied. The case group consisted of 180 patients with RM, defined as two or more consecutive miscarriages (min = 2; max = 8) at up to 20 weeks of gestation, and with clinically confirmed pregnancies and non-viable fetuses. At the time of examination. the women were enrolled from the Genetic Counseling Center at the Kemerovo Regional Clinical Hospital, Kemerovo, Russia, and were not pregnant. Each patient underwent a gynecological examination. We excluded women with a history of medical abortion, birth, and ectopic pregnancies. In addition, we excluded women with endocrine (e.g. diabetes) disorders. To exclude other known causes of spontaneous abortion, the following tests were performed: ultrasound examination of pelvic organs, and karyotyping in women and men. The women’s mean age in the RM group, was 29.6±4.8 (SD) years. The control group comprised 408 fertile women. These women didn’t have a history of spontaneous abortion, or a family history of congenital malformations. They have born, at least, 1-2 healthy children. Women’s mean age at birth of last child was 26.8±5.2 (SD) years. Influence of the intrauterine infection was analyzed on the basis of laboratory tests. Diagnostics of bacterial vaginosis and vulvo-vaginal candidiasis by microscopic examination was conducted. Viral agent infections (herpes simplex virus type 2, cytomegalovirus, human papilloma virus type 16/18), Chlamydia trachomatis, Mycoplasma hominis, Ureaplasma urealyticum, Gardnerella vaginalis and Trichomonas vaginalis were detected by enzyme-linked immunoassay and polymerase chain reaction (PCR). The data were obtained from the medical cards of the surveyed women. All the women gave a written informed consent before participating in the study. Typing of polymorphisms of Thr31Ser (rs41551813, HLA-G*01:03) in exon 2, Leu110Ile (rs12722477, HLA-G*01:04) and 1597 delС (rs41557518, HLA-G*01:05N) in exon 3 HLA-G genes were performed by realtime PCR followed by melting analysis. The study showed that the intrauterine infection was not a risk factor for RM (p = 0.30) in the examined women. It was found that the 110 Ile allele (HLA-G *01:04) was a risk factor for RM both in women with intrauterine infection [ORa = 4.50 (2.41-8.38), p = 2.09e-06], and in women without infection [ORa = 2.46 (1.44-4.21), p = 0.0009]. The cooperative influence of genetic and infections factors with the risk of RM in women was revealed [ORa+f = 3.50 (2.01-6.09), p = 8.78e-06]. Our results will be useful in understanding the molecular mechanisms of immune disorders in fetomaternal interface, and for choosing the strategy of management and treatment in women with RM. ","PeriodicalId":85139,"journal":{"name":"Medical immunology (London, England)","volume":"23 1","pages":"369-380"},"PeriodicalIF":0.0,"publicationDate":"2021-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48642848","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-05-03DOI: 10.15789/1563-0625-ISO-2146
N. M. Agarkov, V. Kolomiets, S. I. Korneeva, E. Moskaleva, K. Makkonen
Metabolic syndrome (MS) is among the main public health challenges worldwide, leading to significant labor losses, increased costs for treatment and rehabilitation of the patients. The aim of the present study was to identify the informative serum interleukins, by determining the odds ratio in elderly patients with MS and hypertension. The main group of 86 patients with MS and arterial hypertension (AH) aged 60-75 years was examined under clinical conditions. The inclusion criteria were as follows: age of 60-75 years, presence of MS, primary hypertension (grade II-III), absence of acute myocardial infarction, malignant neoplasms, disorders of cerebral circulation, kidney failure over last 6 months. Diagnostics of MS and hypertension was carried out in accordance with Expert Guidelines from the Russian Research Society of Cardiology on the MS Diagnosis and Treatment. Our first study of a large range of serum interleukins in elderly patients with MS and hypertension allowed us to reveal the inversely directed changes in pro- and anti-inflammatory cytokine contents. Combined AH/MS in elderly persons is accomplished by sufficient increase of the most proinflammatory cytokines, and vice versa, by significant decrease in anti-inflammatory cytokines in blood serum. This finding clearly points to importance of immunological regulatory systems for initiation of AH with MS at older age. Pro- and anti-inflammatory serum interleukins are actively involved into the AH/MS development in elderly accompanied by their pronounced imbalance. The mentioned immune reactions could underlie the MS/AH condition. High risk of this disorder is connected with changed production of proinflammatory cytokines (IL-8, IL-1β), like as anti-inflammatory serum interleukins (IL-4, IL-10), with predominance of the former. The above interleukins should be considered dominant diagnostic markers of AH/MS in elderly persons. Measurement of serum interleukins and discriminant-based approach allows highly reliable differentiation of elderly patients with AH/MS from similar individuals without this disorder.
{"title":"Informative significance of serum cytokines and their importance for development of metabolic syndrome with arterial hypertension in elderly persons","authors":"N. M. Agarkov, V. Kolomiets, S. I. Korneeva, E. Moskaleva, K. Makkonen","doi":"10.15789/1563-0625-ISO-2146","DOIUrl":"https://doi.org/10.15789/1563-0625-ISO-2146","url":null,"abstract":"Metabolic syndrome (MS) is among the main public health challenges worldwide, leading to significant labor losses, increased costs for treatment and rehabilitation of the patients. The aim of the present study was to identify the informative serum interleukins, by determining the odds ratio in elderly patients with MS and hypertension. The main group of 86 patients with MS and arterial hypertension (AH) aged 60-75 years was examined under clinical conditions. The inclusion criteria were as follows: age of 60-75 years, presence of MS, primary hypertension (grade II-III), absence of acute myocardial infarction, malignant neoplasms, disorders of cerebral circulation, kidney failure over last 6 months. Diagnostics of MS and hypertension was carried out in accordance with Expert Guidelines from the Russian Research Society of Cardiology on the MS Diagnosis and Treatment. Our first study of a large range of serum interleukins in elderly patients with MS and hypertension allowed us to reveal the inversely directed changes in pro- and anti-inflammatory cytokine contents. Combined AH/MS in elderly persons is accomplished by sufficient increase of the most proinflammatory cytokines, and vice versa, by significant decrease in anti-inflammatory cytokines in blood serum. This finding clearly points to importance of immunological regulatory systems for initiation of AH with MS at older age. Pro- and anti-inflammatory serum interleukins are actively involved into the AH/MS development in elderly accompanied by their pronounced imbalance. The mentioned immune reactions could underlie the MS/AH condition. High risk of this disorder is connected with changed production of proinflammatory cytokines (IL-8, IL-1β), like as anti-inflammatory serum interleukins (IL-4, IL-10), with predominance of the former. The above interleukins should be considered dominant diagnostic markers of AH/MS in elderly persons. Measurement of serum interleukins and discriminant-based approach allows highly reliable differentiation of elderly patients with AH/MS from similar individuals without this disorder.","PeriodicalId":85139,"journal":{"name":"Medical immunology (London, England)","volume":"23 1","pages":"303-310"},"PeriodicalIF":0.0,"publicationDate":"2021-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42775575","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-05-03DOI: 10.15789/1563-0625-PCI-2312
N. A. Arsentieva, N. Liubimova, O. K. Batsunov, Z. Korobova, O. Stanevich, A. Lebedeva, E. A. Vorobyov, S. V. Vorobyova, A. N. Kulikov, D. Lioznov, M. A. Sharapova, D. Pevtcov, A. Totolian
COVID-19, an infection caused by the new coronavirus SARS-CoV-2, is associated with a number of pathophysiological mechanisms, mobilizing a wide spectrum of biomolecules, mainly, cytokines The purpose of this study was to evaluate levels of multiple cytokines in blood plasma from the patients with COVID-19 during acute phase of the disease, and upon complete recovery Samples of peripheral blood plasma of 56 patients with COVID-19, 69 convalescents and 10 healthy individuals were examined Concentrations of 46 molecules, such as IL-1α, IL-1β, IL-2, IL-3, IL-4, IL-5, IL-6, IL-7, IL-9, IL-12 (p40), IL-12 (p70), IL-13, IL-15, IL-17A/CTLA8, IL-17-E/IL-25, IL-17F, IL-18, IL-22, IL-27, IFNα2, IFNγ, TNFα, TNFβ/ Lymphotoxin-α (LTA), CCL2/MCP-1, CCL3/MIP-1α, CCL4/MIP-1β, CCL7/MCP-3, CCL11/Eotaxin, CCL22/MDC, CXCL1/GROα, CXCL8/IL-8, CXCL9/MIG, CXCL10/IP-10, CX3CL1/Fractalkine, IL-1ra, IL-10, EGF, FGF-2/FGF-basic, Flt3 Ligand, G-CSF, M-CSF, GM-CSF, PDGF-AA, PDGF-AB/ BB, TGF-α, VEGF-A were measured via xMAP multiplexing technology Significantly increased levels of 18 cytokines were found in blood plasma from COVID-19 patients during acute phase of the disease (as compared to control group), i e , IL-6, IL-7, IL-15, IL-27, TNFα, TNFβ/Lymphotoxin-α (LTA), CCL2/MCP-1, CCL7/MCP-3, CXCL1/GROα, CXCL8/IL-8, CXCL10/IP-10, CXCL9/MIG, IL-1rа, IL-10, M-CSF, GM-CSF, VEGF-A We found a significant decrease of nearly all the mentioned cytokines in recovered patients, in comparison with those who had moderate, severe/extremely severe disease Moreover, we revealed a significantly decreased level of 8 cytokines in plasma from convalescents, as compared with control group, i e , IL-1α, IL-2, IL-9, IL-12 p40, IL-18, CCL22/MDC, Flt3 Ligand, TGF-α Immune response caused by SARS-CoV-2 infection involves multiple cytokines, mostly, with pro-inflammatory effects We have shown for the first time that the convalescence phase is characterized by significantly lower levels of cytokines which regulate cellular differentiation and hematopoiesis (in particular, lymphocytes, T-cells and NK-cells) Over acute phase of the disease, the levels of these cytokines did not change We revealed a significant decrease of most plasma cytokines upon recovery as compared to acute phase On the contrary, acute phase of the disease is accompanied by significant increase of both pro- and antiinflammatory cytokines in blood plasma
{"title":"Plasma cytokines in patients with COVID-19 during acute phase of the disease and following complete recovery","authors":"N. A. Arsentieva, N. Liubimova, O. K. Batsunov, Z. Korobova, O. Stanevich, A. Lebedeva, E. A. Vorobyov, S. V. Vorobyova, A. N. Kulikov, D. Lioznov, M. A. Sharapova, D. Pevtcov, A. Totolian","doi":"10.15789/1563-0625-PCI-2312","DOIUrl":"https://doi.org/10.15789/1563-0625-PCI-2312","url":null,"abstract":"COVID-19, an infection caused by the new coronavirus SARS-CoV-2, is associated with a number of pathophysiological mechanisms, mobilizing a wide spectrum of biomolecules, mainly, cytokines The purpose of this study was to evaluate levels of multiple cytokines in blood plasma from the patients with COVID-19 during acute phase of the disease, and upon complete recovery Samples of peripheral blood plasma of 56 patients with COVID-19, 69 convalescents and 10 healthy individuals were examined Concentrations of 46 molecules, such as IL-1α, IL-1β, IL-2, IL-3, IL-4, IL-5, IL-6, IL-7, IL-9, IL-12 (p40), IL-12 (p70), IL-13, IL-15, IL-17A/CTLA8, IL-17-E/IL-25, IL-17F, IL-18, IL-22, IL-27, IFNα2, IFNγ, TNFα, TNFβ/ Lymphotoxin-α (LTA), CCL2/MCP-1, CCL3/MIP-1α, CCL4/MIP-1β, CCL7/MCP-3, CCL11/Eotaxin, CCL22/MDC, CXCL1/GROα, CXCL8/IL-8, CXCL9/MIG, CXCL10/IP-10, CX3CL1/Fractalkine, IL-1ra, IL-10, EGF, FGF-2/FGF-basic, Flt3 Ligand, G-CSF, M-CSF, GM-CSF, PDGF-AA, PDGF-AB/ BB, TGF-α, VEGF-A were measured via xMAP multiplexing technology Significantly increased levels of 18 cytokines were found in blood plasma from COVID-19 patients during acute phase of the disease (as compared to control group), i e , IL-6, IL-7, IL-15, IL-27, TNFα, TNFβ/Lymphotoxin-α (LTA), CCL2/MCP-1, CCL7/MCP-3, CXCL1/GROα, CXCL8/IL-8, CXCL10/IP-10, CXCL9/MIG, IL-1rа, IL-10, M-CSF, GM-CSF, VEGF-A We found a significant decrease of nearly all the mentioned cytokines in recovered patients, in comparison with those who had moderate, severe/extremely severe disease Moreover, we revealed a significantly decreased level of 8 cytokines in plasma from convalescents, as compared with control group, i e , IL-1α, IL-2, IL-9, IL-12 p40, IL-18, CCL22/MDC, Flt3 Ligand, TGF-α Immune response caused by SARS-CoV-2 infection involves multiple cytokines, mostly, with pro-inflammatory effects We have shown for the first time that the convalescence phase is characterized by significantly lower levels of cytokines which regulate cellular differentiation and hematopoiesis (in particular, lymphocytes, T-cells and NK-cells) Over acute phase of the disease, the levels of these cytokines did not change We revealed a significant decrease of most plasma cytokines upon recovery as compared to acute phase On the contrary, acute phase of the disease is accompanied by significant increase of both pro- and antiinflammatory cytokines in blood plasma","PeriodicalId":85139,"journal":{"name":"Medical immunology (London, England)","volume":"23 1","pages":"311-326"},"PeriodicalIF":0.0,"publicationDate":"2021-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48952758","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-05-03DOI: 10.15789/1563-0625-CAO-2134
L. Androsova, A. Simonov, N. Ponomareva, T. Klyushnik
Determination of inflammatory markers in blood of conventionally healthy people is of interest due to opportunity of detecting diseases at early (preclinical) stages, as well as latent forms of pathological processes. The level of inflammation may serve as an additional criterion to forming control groups in clinical and biological studies. The aim of the study is to identify some inflammatory and autoimmune markers in a group of conventionally healthy people and to conduct a cluster analysis of the data obtained. The study involved 100 apparently healthy people (without clinical signs of infections, somatic, neurological or mental diseases) aged 19 to 88 years. The levels of IL-10, TNFα, IL-6 and autoantibodies to S100b and MBP were determined in blood serum using ELISA. Enzymatic activity of leukocyte elastase (LE) and functional activity of the α1-proteinase inhibitor (α1-PI) were determined spectrophotometrically. Protease inhibitory index (PII) was calculated as the ratio of LE to α1-PI. Cluster analysis, as well as the Shapiro–Wilk, Kruskal–Wallis, and ANOVA methods were used as the main approach to statistical data processing. All the subjects were divided into three clusters, according to their immunological parameters. The selected clusters were statistically significantly different from each other, in terms of LE activity, protease-inhibitory index (PII), as well as IL-10 and TNFα levels. The indices of a distinct cluster (43% of total cohort) are most close to average indices assessed for the general sample, which gives ground to consider the values of immune indicators from this cluster as physiological norm, corresponding to the background immunity state in healthy people. Combination of immunological parameters in two other clusters (30 and 27% of the subjects, respectively) may reflect different variants of inflammatory reactions. These clusters are characterized by multidirectional changes in LE activity and protease-inhibitory index, compared to the standard values, thus suggestive for different variants of latent inflammatory reactivity, which are realized in the patients presented in these clusters. The obtained clusters did not differ by age of the subjects (p = 0.3476), which makes it possible to exclude a significant influence of age on the determined immune parameters, and by gender characteristics (p = 0.7233). The selected clusters did not differ statistically in the functional activity of α1-PI and in the level of autoantibodies to S100b and MBP. Thus, the group of conditionally healthy people is heterogeneous in terms of inflammation markers. Inflammatory reactions of varying severity were detected in about half of the cases. Probably, this may indicate the presence of a latent pathological process and requires a detailed clinical examination.
{"title":"Cluster analysis of blood serum inflammation markers of conditionally healthy people","authors":"L. Androsova, A. Simonov, N. Ponomareva, T. Klyushnik","doi":"10.15789/1563-0625-CAO-2134","DOIUrl":"https://doi.org/10.15789/1563-0625-CAO-2134","url":null,"abstract":"Determination of inflammatory markers in blood of conventionally healthy people is of interest due to opportunity of detecting diseases at early (preclinical) stages, as well as latent forms of pathological processes. The level of inflammation may serve as an additional criterion to forming control groups in clinical and biological studies. The aim of the study is to identify some inflammatory and autoimmune markers in a group of conventionally healthy people and to conduct a cluster analysis of the data obtained. The study involved 100 apparently healthy people (without clinical signs of infections, somatic, neurological or mental diseases) aged 19 to 88 years. The levels of IL-10, TNFα, IL-6 and autoantibodies to S100b and MBP were determined in blood serum using ELISA. Enzymatic activity of leukocyte elastase (LE) and functional activity of the α1-proteinase inhibitor (α1-PI) were determined spectrophotometrically. Protease inhibitory index (PII) was calculated as the ratio of LE to α1-PI. Cluster analysis, as well as the Shapiro–Wilk, Kruskal–Wallis, and ANOVA methods were used as the main approach to statistical data processing. All the subjects were divided into three clusters, according to their immunological parameters. The selected clusters were statistically significantly different from each other, in terms of LE activity, protease-inhibitory index (PII), as well as IL-10 and TNFα levels. The indices of a distinct cluster (43% of total cohort) are most close to average indices assessed for the general sample, which gives ground to consider the values of immune indicators from this cluster as physiological norm, corresponding to the background immunity state in healthy people. Combination of immunological parameters in two other clusters (30 and 27% of the subjects, respectively) may reflect different variants of inflammatory reactions. These clusters are characterized by multidirectional changes in LE activity and protease-inhibitory index, compared to the standard values, thus suggestive for different variants of latent inflammatory reactivity, which are realized in the patients presented in these clusters. The obtained clusters did not differ by age of the subjects (p = 0.3476), which makes it possible to exclude a significant influence of age on the determined immune parameters, and by gender characteristics (p = 0.7233). The selected clusters did not differ statistically in the functional activity of α1-PI and in the level of autoantibodies to S100b and MBP. Thus, the group of conditionally healthy people is heterogeneous in terms of inflammation markers. Inflammatory reactions of varying severity were detected in about half of the cases. Probably, this may indicate the presence of a latent pathological process and requires a detailed clinical examination. ","PeriodicalId":85139,"journal":{"name":"Medical immunology (London, England)","volume":"23 1","pages":"293-302"},"PeriodicalIF":0.0,"publicationDate":"2021-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41599857","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-05-03DOI: 10.15789/1563-0625-FCD-2124
O. Pavlov, S. Chepanov, A. Selutin, M. S. Zainulina, D. Eremeeva, S. Selkov
Activated platelets aggregate with monocytes by binding membrane bound molecules. Platelet-monocyte interaction is considered to underlie pathophysiological mechanisms bridging thrombosis and inflammation. Detection and analysis of platelet-monocyte complexes (PMC) provide means for revealing their physiological and pathogenetic roles and are instrumental in the diagnostics of various pathological conditions including obstetric complications. The aim of the study was to develop the method of quantitative determination of peripheral blood PMC, that preserve phenotypic features of platelets and monocytes, and to reveal their changes by ex vivo analysis. The suggested procedure includes immediate fixation of blood sample, immunocytochemical staining with fluorochrome-conjugated specific antibodies against markers of activation and differentiation followed by lysis of erythrocytes, and flow cytometric analysis. Fourteen samples of peripheral blood from patients with history of pregnancy complication were obtained in first trimester of ongoing pregnancy and analyzed. It was demonstrated that quantitative and qualitative in vivo characteristics of PMC remained unchanged in fixed samples, whereas the number of PMC and expression levels of the markers of platelet and monocyte activation dramatically increased in the unfixed blood. The set of monoclonal antibodies and gating strategies, used in this study, ensure phenotyping and evaluation of percentage/absolute count of PMC in the total monocyte population (CD45+CD14+) and in the subpopulations of classical (CD14+CD16-), intermediate (CD14+CD16+), and non-classical (CD14lowCD16+) monocytes. This approach provides insight into the participation of different monocyte subsets in the formation of PMC and their roles in physiological and pathophysiological processes. In some samples, elevated PMC proportion was observed, accompanied by significant increase in the expression of platelet activation marker CD62P and decrease in the expression of its monocytic ligand CD162. These changes suggested altered activation of PMC and their participation in the pathophysiological mechanisms of some pregnancy complications. Immunophenotyping of PMC affords an opportunity to characterize their proinflammatory, procoagulant and adhesive properties; these results can be used for research and diagnostics. In particular, the method is suitable for detection and phenotyping of PMC in pregnancy complications and other pathological conditions associated with the disorders of hemostasis and thrombosis.
{"title":"Flow cytofluorimetric detection and immunophenotyping of platelet-monocyte complexes in peripheral blood","authors":"O. Pavlov, S. Chepanov, A. Selutin, M. S. Zainulina, D. Eremeeva, S. Selkov","doi":"10.15789/1563-0625-FCD-2124","DOIUrl":"https://doi.org/10.15789/1563-0625-FCD-2124","url":null,"abstract":"Activated platelets aggregate with monocytes by binding membrane bound molecules. Platelet-monocyte interaction is considered to underlie pathophysiological mechanisms bridging thrombosis and inflammation. Detection and analysis of platelet-monocyte complexes (PMC) provide means for revealing their physiological and pathogenetic roles and are instrumental in the diagnostics of various pathological conditions including obstetric complications. The aim of the study was to develop the method of quantitative determination of peripheral blood PMC, that preserve phenotypic features of platelets and monocytes, and to reveal their changes by ex vivo analysis. The suggested procedure includes immediate fixation of blood sample, immunocytochemical staining with fluorochrome-conjugated specific antibodies against markers of activation and differentiation followed by lysis of erythrocytes, and flow cytometric analysis. Fourteen samples of peripheral blood from patients with history of pregnancy complication were obtained in first trimester of ongoing pregnancy and analyzed. It was demonstrated that quantitative and qualitative in vivo characteristics of PMC remained unchanged in fixed samples, whereas the number of PMC and expression levels of the markers of platelet and monocyte activation dramatically increased in the unfixed blood. The set of monoclonal antibodies and gating strategies, used in this study, ensure phenotyping and evaluation of percentage/absolute count of PMC in the total monocyte population (CD45+CD14+) and in the subpopulations of classical (CD14+CD16-), intermediate (CD14+CD16+), and non-classical (CD14lowCD16+) monocytes. This approach provides insight into the participation of different monocyte subsets in the formation of PMC and their roles in physiological and pathophysiological processes. In some samples, elevated PMC proportion was observed, accompanied by significant increase in the expression of platelet activation marker CD62P and decrease in the expression of its monocytic ligand CD162. These changes suggested altered activation of PMC and their participation in the pathophysiological mechanisms of some pregnancy complications. Immunophenotyping of PMC affords an opportunity to characterize their proinflammatory, procoagulant and adhesive properties; these results can be used for research and diagnostics. In particular, the method is suitable for detection and phenotyping of PMC in pregnancy complications and other pathological conditions associated with the disorders of hemostasis and thrombosis.","PeriodicalId":85139,"journal":{"name":"Medical immunology (London, England)","volume":"23 1","pages":"401-410"},"PeriodicalIF":0.0,"publicationDate":"2021-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45602220","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-05-03DOI: 10.15789/1563-0625-IAI-2157
N. Snegireva, E. Sidorova, I. Dyakov, M. Gavrilova, I. Chernyshova, E. Pashkov, O. A. Svitich
IgA is an important component of the mucosal system of the body. It limits penetration of pathogens into the bloodstream. Inflammatory diseases such as Crohn disease and colitis may be associated with disorders of IgA synthesis. Both B1 and B2 cells are a source of IgA in the intestines. Special attention is paid to B1 cells, which are able to respond to T-independent type 2 antigens and produce natural antibodies. B1 cells produce about 50% of the intestinal IgA including specific antibodies to the components of microorganisms contained in the gastrointestinal tract. The mechanism of IgA formation in the T-independent way is not investigated in details. It was suggested that the γδТ-cells promote switching to IgA synthesis by B1 cells. This assumption may be supported by their co-localization with B1 lymphocytes in the intestinal mucosa, as well as participation, along with B1 cells, in formation of the first-line defense against the pathogens. In addition, the both lymphocyte subpopulations evolve during initial ontogenesis, earlier than “classic” В2 and αβT cells. Therefore, it was suggested that γδT lymphocytes may be involved into the processes of induction and/or regulation of IgM and IgA production by B1 cells in response to TH2 antigens.In the present study, we have shown the effect of γδT cells upon generation of IgM- and IgA-forming B1 cells in response to α-1,3-dextran in vitro. We also studied the dynamics of the mRNA expression for IgM- and IgA-heavy chains by the B1 cells at different terms of in vitro culture.It was found that, during co-cultivation of B1 cells with 20% γδT lymphocytes, there is no increase in the number of dextran-specific IgM-producing cells. The B1 cells exhibited an increase of IgM heavy chain mRNA expression in response to dextran but not in co-cultures. Expression of mRNA for IgM heavy chains in co-cultures was decreased compared to non-treated B-cell cultures. Contrary to the earlier assumption, a presence of γδT lymphocytes in culture did not enhance the formation of IgA producents. The obtained data suggest regulatory properties of the γδТ lymphocytes during the B1 cells response to T-independent antigens.
{"title":"IgM- and IgA-response of peritoneal B-1 cells to the TI-2 antigen with the presence of γδT cells in vitro","authors":"N. Snegireva, E. Sidorova, I. Dyakov, M. Gavrilova, I. Chernyshova, E. Pashkov, O. A. Svitich","doi":"10.15789/1563-0625-IAI-2157","DOIUrl":"https://doi.org/10.15789/1563-0625-IAI-2157","url":null,"abstract":"IgA is an important component of the mucosal system of the body. It limits penetration of pathogens into the bloodstream. Inflammatory diseases such as Crohn disease and colitis may be associated with disorders of IgA synthesis. Both B1 and B2 cells are a source of IgA in the intestines. Special attention is paid to B1 cells, which are able to respond to T-independent type 2 antigens and produce natural antibodies. B1 cells produce about 50% of the intestinal IgA including specific antibodies to the components of microorganisms contained in the gastrointestinal tract. The mechanism of IgA formation in the T-independent way is not investigated in details. It was suggested that the γδТ-cells promote switching to IgA synthesis by B1 cells. This assumption may be supported by their co-localization with B1 lymphocytes in the intestinal mucosa, as well as participation, along with B1 cells, in formation of the first-line defense against the pathogens. In addition, the both lymphocyte subpopulations evolve during initial ontogenesis, earlier than “classic” В2 and αβT cells. Therefore, it was suggested that γδT lymphocytes may be involved into the processes of induction and/or regulation of IgM and IgA production by B1 cells in response to TH2 antigens.In the present study, we have shown the effect of γδT cells upon generation of IgM- and IgA-forming B1 cells in response to α-1,3-dextran in vitro. We also studied the dynamics of the mRNA expression for IgM- and IgA-heavy chains by the B1 cells at different terms of in vitro culture.It was found that, during co-cultivation of B1 cells with 20% γδT lymphocytes, there is no increase in the number of dextran-specific IgM-producing cells. The B1 cells exhibited an increase of IgM heavy chain mRNA expression in response to dextran but not in co-cultures. Expression of mRNA for IgM heavy chains in co-cultures was decreased compared to non-treated B-cell cultures. Contrary to the earlier assumption, a presence of γδT lymphocytes in culture did not enhance the formation of IgA producents. The obtained data suggest regulatory properties of the γδТ lymphocytes during the B1 cells response to T-independent antigens. ","PeriodicalId":85139,"journal":{"name":"Medical immunology (London, England)","volume":"23 1","pages":"245-256"},"PeriodicalIF":0.0,"publicationDate":"2021-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44717492","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-05-03DOI: 10.15789/1563-0625-APO-2163
T. Abakumova, T. Gening, S. Gening, I. Antoneeva
Neutrophils play an important role in carcinogenesis, mediating inflammation, immunosuppression and metastasis. A dual role of neutrophils in regulation of angiogenesis has been shown. Endometrial cancer is the most common malignant neoplasm of the female reproductive system. To assess the cellular angiogenic potential, we determined the levels of inflammatory and angiogenic cytokines (VEGF-A, IL-17A, IL-1β, IL-6) in cell lysate of peripheral blood neutrophils in the patients with endometrial cancer, and with uterine myoma (comparison group). Expression of the nuclear factor-kB was determined. In nuclear fraction of neutrophils. The neutrophil-to-lymphocyte ratio (NLR) was assessed in the studied groups. Statistical processing of the obtained data was carried out using Statistica 10 software. We have not found any significant changes in NLR in endometrial cancer, compared with controls and the uterine myoma groups. Expression of NF-kB and VEGF was increased as compared to the control for all the studied stages of endometrial cancer and in uterine myoma. There was a change in NF-kB level in neutrophils, depending on the tumor differentiation grade. A regression relationship was found between the content of VEGF and NF-kB in neutrophils. We have found increased IL-1β and IL-6 levels in neutrophils of the uterine myoma patients, and at different stages of endometrial cancer compared with control. The IL-1β level was higher in neutrophils of the patients with intermediate and high tumor grade, compared to low-grade cases. IL-17A expression in the neutrophil lysate was significantly reduced in uterine myoma and at different stages of endometrial cancer, as compared with controls. There was a moderate inverse correlation between the contents of VEGF and IL-6 in neutrophils (r = -0.426, p = 0.001); a remarkable inverse relationship between VEGF and IL-17A (r = -0.615, p < 0.001). The combination of IL-6 and IL-17A levels in the neutrophils lysate (according to the results of multivariate analysis) may be used for the differential diagnosis of endometrial cancer and uterine myoma. Thus, the differences in the expression of inflammatory and angiogenic cytokines included in NF-kB-dependent signaling, may point to acquisition of pro-tumor functions by neutrophils during the endometrial cancer progression.
{"title":"Angiogenic potential of circulating blood neutrophils in endometrial cancer","authors":"T. Abakumova, T. Gening, S. Gening, I. Antoneeva","doi":"10.15789/1563-0625-APO-2163","DOIUrl":"https://doi.org/10.15789/1563-0625-APO-2163","url":null,"abstract":"Neutrophils play an important role in carcinogenesis, mediating inflammation, immunosuppression and metastasis. A dual role of neutrophils in regulation of angiogenesis has been shown. Endometrial cancer is the most common malignant neoplasm of the female reproductive system. To assess the cellular angiogenic potential, we determined the levels of inflammatory and angiogenic cytokines (VEGF-A, IL-17A, IL-1β, IL-6) in cell lysate of peripheral blood neutrophils in the patients with endometrial cancer, and with uterine myoma (comparison group). Expression of the nuclear factor-kB was determined. In nuclear fraction of neutrophils. The neutrophil-to-lymphocyte ratio (NLR) was assessed in the studied groups. Statistical processing of the obtained data was carried out using Statistica 10 software. We have not found any significant changes in NLR in endometrial cancer, compared with controls and the uterine myoma groups. Expression of NF-kB and VEGF was increased as compared to the control for all the studied stages of endometrial cancer and in uterine myoma. There was a change in NF-kB level in neutrophils, depending on the tumor differentiation grade. A regression relationship was found between the content of VEGF and NF-kB in neutrophils. We have found increased IL-1β and IL-6 levels in neutrophils of the uterine myoma patients, and at different stages of endometrial cancer compared with control. The IL-1β level was higher in neutrophils of the patients with intermediate and high tumor grade, compared to low-grade cases. IL-17A expression in the neutrophil lysate was significantly reduced in uterine myoma and at different stages of endometrial cancer, as compared with controls. There was a moderate inverse correlation between the contents of VEGF and IL-6 in neutrophils (r = -0.426, p = 0.001); a remarkable inverse relationship between VEGF and IL-17A (r = -0.615, p < 0.001). The combination of IL-6 and IL-17A levels in the neutrophils lysate (according to the results of multivariate analysis) may be used for the differential diagnosis of endometrial cancer and uterine myoma. Thus, the differences in the expression of inflammatory and angiogenic cytokines included in NF-kB-dependent signaling, may point to acquisition of pro-tumor functions by neutrophils during the endometrial cancer progression. ","PeriodicalId":85139,"journal":{"name":"Medical immunology (London, England)","volume":"23 1","pages":"339-344"},"PeriodicalIF":0.0,"publicationDate":"2021-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42179358","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-05-03DOI: 10.15789/1563-0625-MSC-2128
K. Yurova, E. Melashchenko, O. G. Khasiakhmatova, V. Malashchenko, O. Melashchenko, E. Shunkin, I. K. Norkin, I. Khlusov, L. Litvinova
Molecular genetic mechanisms, signaling pathways, cultural conditions, factors, and markers of osteogenic differentiation of mesenchymal stem cells (MSC) are actively studied despite numerous works in this area of cellular technologies. This is largely due to the accumulating contradictions in seemingly classical knowledge, as well as permanent updating of the results in the field. In this regard, we focused on the main classical concepts and some new factors and mechanisms that have a noticeable regulatory effect on the differentiation potential of postnatal MSCs. The present review considers the significance of MSC sources for their differentiation capacity, as well as the role of the cellular microenvironment. The issues of classification, terminology, and functional activity of MSCs from various sources are discussed. The paracrine potential of MSCs in tissue regeneration has been considered; sufficient importance of inflammation in osteogenesis is noted, in particular, the presence of inflammatory cytokines and chemokines in the lesion focus, produced not only by microenvironmental cells but also by blood cells, including mononuclear leukocytes, migrating to the affected site. An important role in this review is given to biomechanical signals and to influence of conformational changes in cell cytoskeleton (cell shape) upon MSC differentiation, since the morphological features of cells and the structure of cytoskeleton are modulated by interactions of the cell surface with environmental factors, including hydrostatic pressure, fluid flow, compression/stretching loads. The data are presented concerning elasticity of extracellular matrix being a determining factor of cell differentiation. We conclude that one should switch from point studies of individual gene effects to multiple measurements of the gene-regulatory profile and biomolecules responsible for multiple, still poorly studied osteogenic factors of endogenous and exogenous origin. Among cornerstones in future (epi)genetic studies will be to decide if osteomodulatory effects are realized through specific signaling pathways and/or via cross-signaling with known genes controlling osteogenic differentiation of MSCs.
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