Abdallah S Abdelazem, Azza Ali Khalil, Dalia Ghareeb, Ahmad Sallam Soliman, Hanaa M El Maghraby, Nagwan A Ismail, Samia Hussein
Bronchial asthma (BA) is increasing among Egyptian children. It is affected by multiple factors including genetic ones. In the current study, we assessed the relationship between interleukin-17 (IL-17) genotypes and the occurrence of BA among Egyptian children. This case-control study included 100 participants. Group I (the control group) comprised 50 healthy subjects. Group II (the asthmatic group) comprised 50 subjects diagnosed with atopic asthma according to the Global Initiative for Asthma. Measurement of serum Ig E and eosinophilic count was performed. Detection of single nucleotide polymorphism rs2275913 of IL-17 gene by restriction fragment length polymorphism-polymerase chain reaction was conducted. GA and AA genotypes were more frequent in the asthmatic group compared to the control group (P = 0.03 and 0.01, respectively). Subjects carrying GA and AA genotypes were more susceptible to have asthma [odds ratio (OR) = 2.21, 95% confidence interval (CI) = 1.14-9.94, P = 0.03; OR = 7.78, 95% CI = 1.59-38.3, P = 0.01, respectively]. The A allele was higher in the asthmatic group (33%) compared to the control group (10%). A allele carriers were more susceptible to have asthma (OR = 4.43, 95% CI = 2.04-9.82 and P < 0.001). Immunoglobulin E (IgE) levels and eosinophil percentages were higher among the carriers of GA and AA genotypes when compared with the GG genotype. All pulmonary function tests were significantly lower among carriers of AA genotype compared with GG genotype. An A allele carrier, AA genotype, increased IgE level, and eosinophil level were significant predictors for occurrence of asthma (P = 0.01, 0.02, 0.004, and 0.01). In conclusion, AA genotype carriers and A allele carriers of the IL-17 gene are more likely to have asthma compared with controls.
支气管哮喘(BA)在埃及儿童中的发病率越来越高。它受到包括遗传因素在内的多种因素的影响。在本研究中,我们评估了白细胞介素-17(IL-17)基因型与埃及儿童支气管哮喘发病率之间的关系。这项病例对照研究包括 100 名参与者。第一组(对照组)包括 50 名健康受试者。第二组(哮喘组)由 50 名根据全球哮喘倡议被诊断为特应性哮喘的受试者组成。测量血清 Ig E 和嗜酸性粒细胞计数。通过限制性片段长度多态性聚合酶链反应检测了 IL-17 基因的单核苷酸多态性 rs2275913。与对照组相比,GA 和 AA 基因型在哮喘组中更为常见(P = 0.03 和 0.01)。携带 GA 和 AA 基因型的受试者更易患哮喘[几率比(OR)= 2.21,95% 置信区间(CI)= 1.14-9.94,P = 0.03;OR = 7.78,95% CI = 1.59-38.3,P = 0.01]。与对照组(10%)相比,哮喘组的 A 等位基因携带者比例更高(33%)。A 等位基因携带者更容易患哮喘(OR = 4.43,95% CI = 2.04-9.82,P < 0.001)。与 GG 基因型相比,GA 和 AA 基因型携带者的免疫球蛋白 E(IgE)水平和嗜酸性粒细胞百分比更高。与 GG 基因型相比,AA 基因型携带者的所有肺功能测试结果均明显降低。A 等位基因携带者、AA 基因型、IgE 水平升高和嗜酸性粒细胞水平升高是哮喘发生的重要预测因素(P = 0.01、0.02、0.004 和 0.01)。总之,与对照组相比,IL-17 基因的 AA 基因型携带者和 A 等位基因携带者更容易患哮喘。
{"title":"<i>Interleukin-17</i> Genotypes in Egyptian Asthmatic Children at Zagazig University Hospitals.","authors":"Abdallah S Abdelazem, Azza Ali Khalil, Dalia Ghareeb, Ahmad Sallam Soliman, Hanaa M El Maghraby, Nagwan A Ismail, Samia Hussein","doi":"10.1089/jir.2024.0098","DOIUrl":"https://doi.org/10.1089/jir.2024.0098","url":null,"abstract":"<p><p>Bronchial asthma (BA) is increasing among Egyptian children. It is affected by multiple factors including genetic ones. In the current study, we assessed the relationship between <i>interleukin-17</i> (<i>IL-17</i>) genotypes and the occurrence of BA among Egyptian children. This case-control study included 100 participants. Group I (the control group) comprised 50 healthy subjects. Group II (the asthmatic group) comprised 50 subjects diagnosed with atopic asthma according to the Global Initiative for Asthma. Measurement of serum Ig E and eosinophilic count was performed. Detection of single nucleotide polymorphism <i>rs2275913 of IL-17</i> gene by restriction fragment length polymorphism-polymerase chain reaction was conducted. GA and AA genotypes were more frequent in the asthmatic group compared to the control group (<i>P</i> = 0.03 and 0.01, respectively). Subjects carrying GA and AA genotypes were more susceptible to have asthma [odds ratio (OR) = 2.21, 95% confidence interval (CI) = 1.14-9.94, <i>P</i> = 0.03; OR = 7.78, 95% CI = 1.59-38.3, <i>P</i> = 0.01, respectively]. The A allele was higher in the asthmatic group (33%) compared to the control group (10%). A allele carriers were more susceptible to have asthma (OR = 4.43, 95% CI = 2.04-9.82 and <i>P</i> < 0.001). Immunoglobulin E (IgE) levels and eosinophil percentages were higher among the carriers of GA and AA genotypes when compared with the GG genotype. All pulmonary function tests were significantly lower among carriers of AA genotype compared with GG genotype. An A allele carrier, AA genotype, increased IgE level, and eosinophil level were significant predictors for occurrence of asthma (<i>P</i> = 0.01, 0.02, 0.004, and 0.01). In conclusion, AA genotype carriers and A allele carriers of the <i>IL-17</i> gene are more likely to have asthma compared with controls.</p>","PeriodicalId":16261,"journal":{"name":"Journal of Interferon and Cytokine Research","volume":null,"pages":null},"PeriodicalIF":1.9,"publicationDate":"2024-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141788318","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cinthia A Molina-Flores, José G Pinales-Rangel, Sandra K Santuario-Facio, Arguiñe I Urraza-Robledo, María E Gutiérrez-Pérez, Alberto A Miranda-Pérez, Francisco C López-Márquez
{"title":"Role of Proinflammatory Cytokines and Genetic Factors Related to Metabolic Alterations in People Living with HIV/AIDS.","authors":"Cinthia A Molina-Flores, José G Pinales-Rangel, Sandra K Santuario-Facio, Arguiñe I Urraza-Robledo, María E Gutiérrez-Pérez, Alberto A Miranda-Pérez, Francisco C López-Márquez","doi":"10.1089/jir.2024.0052","DOIUrl":"https://doi.org/10.1089/jir.2024.0052","url":null,"abstract":"","PeriodicalId":16261,"journal":{"name":"Journal of Interferon and Cytokine Research","volume":null,"pages":null},"PeriodicalIF":1.9,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141476791","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
This pilot study aimed to evaluate the immunomodulatory effect of placental mesenchymal stem/stromal cells (MSCs) on peripheral blood mononuclear cells (PBMCs) from patients with hidradenitis suppurativa (HS). Blood samples were collected from 3 healthy and 3 patients with HS. Isolated PBMCs were stained with carboxyfluorescein succinimidyl ester (CFSE) and stimulated with phorbol 12-myristate 13-acetate (PMA)/Ionomycin solution. The PBMCs of patients with HS were co-cultured with naïve MSCs (n-MSCs), activated with tumor necrosis factor (TNF)-α (10 ng/mL) and interferon (IFN)-γ (10 ng/mL) MSCs (a-MSCs), or adalimumab (30 μg/mL). The division index (proliferation inhibition) of PBMCs was analyzed by flow cytometry using the Proliferation Modeling tool after 5 days of coculture. The relative inflammatory gene expression dynamics and cytokine secretion were quantified in triplicate using real-time polymerase chain reaction (PCR) and Luminex assays. PBMCs from the HS control group showed statistically significant increases in interleukin (IL)-6 and IFN-γ cytokine concentrations and IL-17A gene expression when compared with healthy subjects. Statistically significant reduction of the division index was found in the a-MSCs group (P = 0.04). Also, the Luminex assay revealed significantly reduced proinflammatory cytokine concentrations of IL-9 (P = 0.022) and IL-17A (P = 0.022) in the a-MSCs group with the same trend of numerical lowering in n-MSCs group when compared to HS control. The results of real-time PCR revealed a numerical increase in the expression of the IL-1β, IL-36α, and TNF-α genes in both the a-MSCs and n-MSCs groups compared with the HS control. In conclusion, our findings suggest that MSCs can effectively curb PBMCs proliferation and suppress the production of inflammatory cytokines. Moreover, the preactivation of MSCs with IFN-γ and TNF-α before use can enhance their therapeutic effectiveness. Nevertheless, a larger sample size is imperative to validate these results.
{"title":"Activated and Naïve Allogenic Human Placental Mesenchymal Stromal Cells Exert an Immunomodulatory Effect on Hidradenitis Suppurativa Patient Peripheral Blood Mononuclear Cells.","authors":"Vaiva Jariene, Paulius Valiukevicius, Justinas Maciulaitis, Ugne Kuzaityte, Ruta Insodaite, Ieva Ciapiene, Romaldas Maciulaitis, Skaidra Valiukeviciene","doi":"10.1089/jir.2024.0035","DOIUrl":"10.1089/jir.2024.0035","url":null,"abstract":"<p><p>This pilot study aimed to evaluate the immunomodulatory effect of placental mesenchymal stem/stromal cells (MSCs) on peripheral blood mononuclear cells (PBMCs) from patients with hidradenitis suppurativa (HS). Blood samples were collected from 3 healthy and 3 patients with HS. Isolated PBMCs were stained with carboxyfluorescein succinimidyl ester (CFSE) and stimulated with phorbol 12-myristate 13-acetate (PMA)/Ionomycin solution. The PBMCs of patients with HS were co-cultured with naïve MSCs (n-MSCs), activated with tumor necrosis factor (TNF)-α (10 ng/mL) and interferon (IFN)-γ (10 ng/mL) MSCs (a-MSCs), or adalimumab (30 μg/mL). The division index (proliferation inhibition) of PBMCs was analyzed by flow cytometry using the Proliferation Modeling tool after 5 days of coculture. The relative inflammatory gene expression dynamics and cytokine secretion were quantified in triplicate using real-time polymerase chain reaction (PCR) and Luminex assays. PBMCs from the HS control group showed statistically significant increases in interleukin (IL)-6 and IFN-γ cytokine concentrations and <i>IL-17A</i> gene expression when compared with healthy subjects. Statistically significant reduction of the division index was found in the a-MSCs group (<i>P</i> = 0.04). Also, the Luminex assay revealed significantly reduced proinflammatory cytokine concentrations of IL-9 (<i>P</i> = 0.022) and IL-17A (<i>P</i> = 0.022) in the a-MSCs group with the same trend of numerical lowering in n-MSCs group when compared to HS control. The results of real-time PCR revealed a numerical increase in the expression of the <i>IL-1β, IL-36α</i>, and <i>TNF-α</i> genes in both the a-MSCs and n-MSCs groups compared with the HS control. In conclusion, our findings suggest that MSCs can effectively curb PBMCs proliferation and suppress the production of inflammatory cytokines. Moreover, the preactivation of MSCs with IFN-γ and TNF-α before use can enhance their therapeutic effectiveness. Nevertheless, a larger sample size is imperative to validate these results.</p>","PeriodicalId":16261,"journal":{"name":"Journal of Interferon and Cytokine Research","volume":null,"pages":null},"PeriodicalIF":1.9,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140859412","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
India saw a spike in COVID-19 cases in early 2023, and this wave of infection was attributed to XBB sublineages of SARS-CoV-2 Omicron variant. The impact of XBB wave was significantly shorter with low burden of severe cases or hospitalization as compared with previous SARS-CoV-2 variants of concern. Although a combination of old and new mutations in the spike region of XBB.1.16 variant led to a drastic reduction in the ability of antibodies from prior immunity to neutralize this virus, additional nonspike mutations suggested a possible change in its ability to suppress innate immune responses. In this study, we tested the sensitivity of Delta, BA.2.75, and XBB.1.16 variants to interferon-β (IFN-β) treatment and found that XBB.1.16 variant was most sensitive to IFN-β. We next tested the ability of serum antibodies from healthy individuals to neutralize XBB.1.16. We showed that most of the individuals with hybrid immunity maintained a low but significant level of neutralizing antibodies to XBB.1.16 variant. Therefore, our observations indicated that both hybrid immunity because of natural infection and enhanced sensitivity to IFNs may have contributed to the low impact of XBB.1.16 infections in India.
{"title":"The Effective Inhibitory Concentration of Interferon-β Correlates with Infectivity and Replication Fitness of SARS-CoV-2 Variants.","authors":"Janmejay Singh, Anbalagan Anantharaj, Parveen Kumar, Rajesh Pandey, Anil Kumar Pandey, Guruprasad R Medigeshi","doi":"10.1089/jir.2024.0016","DOIUrl":"10.1089/jir.2024.0016","url":null,"abstract":"<p><p>India saw a spike in COVID-19 cases in early 2023, and this wave of infection was attributed to XBB sublineages of SARS-CoV-2 Omicron variant. The impact of XBB wave was significantly shorter with low burden of severe cases or hospitalization as compared with previous SARS-CoV-2 variants of concern. Although a combination of old and new mutations in the spike region of XBB.1.16 variant led to a drastic reduction in the ability of antibodies from prior immunity to neutralize this virus, additional nonspike mutations suggested a possible change in its ability to suppress innate immune responses. In this study, we tested the sensitivity of Delta, BA.2.75, and XBB.1.16 variants to interferon-β (IFN-β) treatment and found that XBB.1.16 variant was most sensitive to IFN-β. We next tested the ability of serum antibodies from healthy individuals to neutralize XBB.1.16. We showed that most of the individuals with hybrid immunity maintained a low but significant level of neutralizing antibodies to XBB.1.16 variant. Therefore, our observations indicated that both hybrid immunity because of natural infection and enhanced sensitivity to IFNs may have contributed to the low impact of XBB.1.16 infections in India.</p>","PeriodicalId":16261,"journal":{"name":"Journal of Interferon and Cytokine Research","volume":null,"pages":null},"PeriodicalIF":1.9,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140335914","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-01Epub Date: 2024-05-17DOI: 10.1089/jir.2024.0057
Amin Golshah, Masoud Sadeghi, Edris Sadeghi
Obstructive sleep apnea (OSA) is a chronic inflammatory disease characterized by partial or complete upper airway obstruction during sleep. We aimed to evaluate serum/plasma levels of several cytokines (interleukin [IL]-6, IL-12, IL-17, IL-18, and IL-23) in a systematic review meta-analysis in both adults and children with OSA compared with controls. We conducted a comprehensive search of 4 digital databases (PubMed, Web of Science, Scopus, and Cochrane Library) up until October 19, 2023, without any limitations. For our meta-analysis, we used Review Manager, version 5.3, and displayed the data as the standardized mean difference (SMD) and 95% confidence interval (CI) to assess the correlation between cytokine levels and OSA. We utilized Comprehensive Meta-Analysis version 3.0 software to conduct bias analyses, meta-regression, and sensitivity analyses. From 1881 records, 84 articles were included in the systematic review and meta-analysis. In adults, the pooled SMDs for IL-6 level were 0.79 (P value < 0.00001), for IL-17 level were 0.74 (P value = 0.14), and for IL-18 level were 0.43 (P value = 0.00002). In children, the pooled SMD for IL-6 was 1.10 (P value < 0.00001), for IL-12 was 0.47 (P value = 0.10), for IL-17 was 2.21 (a P value = 0.24), for IL-18 was 0.19 (P value = 0.07), and for IL-23 was 2.46 (P value < 0.0001). The subgroup analysis showed that the ethnicity, mean body mass index, and mean apnea-hypopnea index for IL-6 levels in adults and the ethnicity for IL-6 levels in children were effective factors in the pooled SMD. The findings of the trial sequential analysis revealed that adequate evidence has been obtained. The analysis of IL levels in adults and children with OSA compared with those without OSA revealed significant differences. In adults, IL-6 and IL-18 levels were significantly higher in the OSA group, while in children, only IL-6 and IL-23 levels were significantly elevated.
阻塞性睡眠呼吸暂停(OSA)是一种慢性炎症性疾病,其特点是睡眠时上气道部分或完全阻塞。我们的目的是通过系统综述荟萃分析评估几种细胞因子(白细胞介素 [IL]-6、IL-12、IL-17、IL-18 和 IL-23)的血清/血浆水平,将成人和儿童 OSA 患者与对照组进行比较。截至 2023 年 10 月 19 日,我们对 4 个数字数据库(PubMed、Web of Science、Scopus 和 Cochrane Library)进行了全面检索,没有任何限制。在进行荟萃分析时,我们使用了5.3版的Review Manager,并将数据显示为标准化平均差(SMD)和95%置信区间(CI),以评估细胞因子水平与OSA之间的相关性。我们使用 Comprehensive Meta-Analysis 3.0 版软件进行了偏倚分析、元回归和敏感性分析。在1881条记录中,有84篇文章被纳入系统综述和荟萃分析。在成人中,IL-6水平的集合SMD为0.79(P值<0.00001),IL-17水平的集合SMD为0.74(P值=0.14),IL-18水平的集合SMD为0.43(P值=0.00002)。在儿童中,IL-6的集合SMD为1.10(P值<0.00001),IL-12为0.47(P值=0.10),IL-17为2.21(P值=0.24),IL-18为0.19(P值=0.07),IL-23为2.46(P值<0.0001)。亚组分析表明,成人IL-6水平的种族、平均体重指数和平均呼吸暂停-低通气指数以及儿童IL-6水平的种族是影响集合SMD的有效因素。试验序列分析结果显示,已获得了充分的证据。对患有 OSA 的成人和儿童的 IL 水平与未患有 OSA 的成人和儿童的 IL 水平进行的分析表明,两者之间存在显著差异。在成人中,OSA组的IL-6和IL-18水平显著升高,而在儿童中,只有IL-6和IL-23水平显著升高。
{"title":"Evaluation of Serum/Plasma Levels of Interleukins (IL-6, IL-12, IL-17, IL-18, and IL-23) in Adults and Children with Obstructive Sleep Apnea: A Systematic Review, Meta-Analysis, and Trial Sequential Analysis.","authors":"Amin Golshah, Masoud Sadeghi, Edris Sadeghi","doi":"10.1089/jir.2024.0057","DOIUrl":"10.1089/jir.2024.0057","url":null,"abstract":"<p><p>Obstructive sleep apnea (OSA) is a chronic inflammatory disease characterized by partial or complete upper airway obstruction during sleep. We aimed to evaluate serum/plasma levels of several cytokines (interleukin [IL]-6, IL-12, IL-17, IL-18, and IL-23) in a systematic review meta-analysis in both adults and children with OSA compared with controls. We conducted a comprehensive search of 4 digital databases (PubMed, Web of Science, Scopus, and Cochrane Library) up until October 19, 2023, without any limitations. For our meta-analysis, we used Review Manager, version 5.3, and displayed the data as the standardized mean difference (SMD) and 95% confidence interval (CI) to assess the correlation between cytokine levels and OSA. We utilized Comprehensive Meta-Analysis version 3.0 software to conduct bias analyses, meta-regression, and sensitivity analyses. From 1881 records, 84 articles were included in the systematic review and meta-analysis. In adults, the pooled SMDs for IL-6 level were 0.79 (<i>P</i> value < 0.00001), for IL-17 level were 0.74 (<i>P</i> value = 0.14), and for IL-18 level were 0.43 (<i>P</i> value = 0.00002). In children, the pooled SMD for IL-6 was 1.10 (<i>P</i> value < 0.00001), for IL-12 was 0.47 (<i>P</i> value = 0.10), for IL-17 was 2.21 (a <i>P</i> value = 0.24), for IL-18 was 0.19 (<i>P</i> value = 0.07), and for IL-23 was 2.46 (<i>P</i> value < 0.0001). The subgroup analysis showed that the ethnicity, mean body mass index, and mean apnea-hypopnea index for IL-6 levels in adults and the ethnicity for IL-6 levels in children were effective factors in the pooled SMD. The findings of the trial sequential analysis revealed that adequate evidence has been obtained. The analysis of IL levels in adults and children with OSA compared with those without OSA revealed significant differences. In adults, IL-6 and IL-18 levels were significantly higher in the OSA group, while in children, only IL-6 and IL-23 levels were significantly elevated.</p>","PeriodicalId":16261,"journal":{"name":"Journal of Interferon and Cytokine Research","volume":null,"pages":null},"PeriodicalIF":1.9,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140957876","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Tahmineh Safaie, Kham R Trinh, Alex Vasuthasawat, Sherie L Morrison, David R Stover
{"title":"An Anti-CD138-Targeted Interferon-Alpha Has Broad Efficacy in Solid Tumors Through Direct Tumor Cell Killing and Intratumoral Immune Modulation.","authors":"Tahmineh Safaie, Kham R Trinh, Alex Vasuthasawat, Sherie L Morrison, David R Stover","doi":"10.1089/jir.2024.0099","DOIUrl":"https://doi.org/10.1089/jir.2024.0099","url":null,"abstract":"","PeriodicalId":16261,"journal":{"name":"Journal of Interferon and Cytokine Research","volume":null,"pages":null},"PeriodicalIF":1.9,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141476788","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-01Epub Date: 2024-05-13DOI: 10.1089/jir.2024.0018
Mojtaba Shohan, Mohammad Reza Mahmoudian-Sani, Ali Saeedi-Boroujeni, Sara Iranparast, Roohangiz Nashibi, Farhad Abolnezhadian, Farid Yousefi, Seyed Mohammad Alavi, Bahman Cheraghian, Ali Khodadadi
As an antibody-based therapy, plasma therapy has been used as an emergency therapeutic strategy against severe acute respiratory syndrome coronavirus type 2 infection. Due to the critical role of macrophages in coronavirus disease-19 (COVID-19)-associated hyperinflammation, the main objective of this study was to assess the effect of plasma transfusion on the expression levels of the inflammatory biomarkers involved in activation and pulmonary infiltration of macrophages. The target population included 50 severe hospitalized COVID-19 patients who were randomly assigned into 2 groups, including intervention and control. Serum levels of chemokine (C-C motif) ligand (CCL)-2, CCL-3, tumor necrosis factor (TNF)-α, and interleukin (IL)-6 were measured by enzyme-linked immunosorbent assay. Moreover, quantitative real-time polymerase chain reaction (PCR) was carried out to assess the relative expression of nuclear factor (NF)-κB1, NF-κB2, nuclear factor erythroid 2 p45-related factor 2 (NRF-2), and thioredoxin-interacting protein genes. Sampling was done at baseline and 72 h after receiving plasma. The intervention group demonstrated significantly lower serum levels of IL-6, TNF-α, and CCL-3. In addition, real-time PCR data analyses showed that the relative expression of NF-κB2 was significantly declined in the patients who received plasma. The use of convalescent plasma probably has a significant inhibitory effect on the cytokines, chemokines, and inflammatory genes related to macrophage activation, which are closely associated with the worsening of clinical outcomes in severe COVID-19.
{"title":"The Effects of Convalescent Plasma Transfusion on Serum Levels of Macrophage-Associated Inflammatory Biomarkers in Patients with Severe COVID-19.","authors":"Mojtaba Shohan, Mohammad Reza Mahmoudian-Sani, Ali Saeedi-Boroujeni, Sara Iranparast, Roohangiz Nashibi, Farhad Abolnezhadian, Farid Yousefi, Seyed Mohammad Alavi, Bahman Cheraghian, Ali Khodadadi","doi":"10.1089/jir.2024.0018","DOIUrl":"10.1089/jir.2024.0018","url":null,"abstract":"<p><p>As an antibody-based therapy, plasma therapy has been used as an emergency therapeutic strategy against severe acute respiratory syndrome coronavirus type 2 infection. Due to the critical role of macrophages in coronavirus disease-19 (COVID-19)-associated hyperinflammation, the main objective of this study was to assess the effect of plasma transfusion on the expression levels of the inflammatory biomarkers involved in activation and pulmonary infiltration of macrophages. The target population included 50 severe hospitalized COVID-19 patients who were randomly assigned into 2 groups, including intervention and control. Serum levels of chemokine (C-C motif) ligand (CCL)-2, CCL-3, tumor necrosis factor (TNF)-α, and interleukin (IL)-6 were measured by enzyme-linked immunosorbent assay. Moreover, quantitative real-time polymerase chain reaction (PCR) was carried out to assess the relative expression of nuclear factor (NF)-κB1, NF-κB2, nuclear factor erythroid 2 p45-related factor 2 (NRF-2), and thioredoxin-interacting protein genes. Sampling was done at baseline and 72 h after receiving plasma. The intervention group demonstrated significantly lower serum levels of IL-6, TNF-α, and CCL-3. In addition, real-time PCR data analyses showed that the relative expression of NF-κB2 was significantly declined in the patients who received plasma. The use of convalescent plasma probably has a significant inhibitory effect on the cytokines, chemokines, and inflammatory genes related to macrophage activation, which are closely associated with the worsening of clinical outcomes in severe COVID-19.</p>","PeriodicalId":16261,"journal":{"name":"Journal of Interferon and Cytokine Research","volume":null,"pages":null},"PeriodicalIF":1.9,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140911849","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sepsis is a clinically life-threatening syndrome, and acute lung injury is the earliest and most serious complication. We aimed to assess the role of kruppel-like factor 13 (KLF13) in lipopolysaccharide (LPS)-induced human alveolar type II epithelial cell damage and to reveal the possible mechanism related to peroxisome proliferator-activated receptor-γ co-activator 1-α (PGC-1α). In LPS-treated A549 cells with or without KLF13 overexpression or PGC-1α knockdown, cell viability was measured by a cell counting kit-8 assay. Enzyme-linked immunosorbent assay kits detected the levels of inflammatory factors, and terminal deoxynucleotidyl transferase dUTP nick-end labeling staining measured cell apoptosis. Besides, mitochondrial reactive oxygen species (MitoSOX) and mitochondrial membrane potential were detected using MitoSOX red- and JC-1 staining. Expression of proteins related to mitochondrial quality control (MQC) was evaluated by western blot. Co-immunoprecipitation (Co-IP) assay was used to analyze the interaction between KLF13 and PGC-1α. Results indicated that KLF13 was highly expressed in LPS-treated A549 cells. KLF13 upregulation elevated the viability and reduced the levels of inflammatory factors in A549 cells exposed to LPS. Moreover, KLF13 gain-of-function inhibited LPS-induced apoptosis of A549 cells, accompanied by upregulated BCL2 expression and downregulated Bax and cleaved caspase3 expression. Furthermore, MQC was improved by KLF13 overexpression, as evidenced by decreased MitoSOX, JC-1 monomers and increased JC-1 aggregates, coupled with the changes of proteins related to MQC. In addition, Co-IP assay confirmed the interaction between KLF13 and PGC-1α. PGC-1α deficiency restored the impacts of KLF13 upregulation on the inflammation, apoptosis, and MQC in LPS-treated A549 cells. In conclusion, KLF13 attenuated LPS-induced alveolar epithelial cell inflammation and apoptosis by regulating MQC via binding PGC-1α.
{"title":"KLF13 Attenuates Lipopolysaccharide-Induced Alveolar Epithelial Cell Damage by Regulating Mitochondrial Quality Control via Binding PGC-1α.","authors":"Qiong Xi, Lin Liu, Qin Zhao, Shan Zhu","doi":"10.1089/jir.2023.0234","DOIUrl":"https://doi.org/10.1089/jir.2023.0234","url":null,"abstract":"<p><p>Sepsis is a clinically life-threatening syndrome, and acute lung injury is the earliest and most serious complication. We aimed to assess the role of kruppel-like factor 13 (KLF13) in lipopolysaccharide (LPS)-induced human alveolar type II epithelial cell damage and to reveal the possible mechanism related to peroxisome proliferator-activated receptor-γ co-activator 1-α (PGC-1α). In LPS-treated A549 cells with or without KLF13 overexpression or PGC-1α knockdown, cell viability was measured by a cell counting kit-8 assay. Enzyme-linked immunosorbent assay kits detected the levels of inflammatory factors, and terminal deoxynucleotidyl transferase dUTP nick-end labeling staining measured cell apoptosis. Besides, mitochondrial reactive oxygen species (MitoSOX) and mitochondrial membrane potential were detected using MitoSOX red- and JC-1 staining. Expression of proteins related to mitochondrial quality control (MQC) was evaluated by western blot. Co-immunoprecipitation (Co-IP) assay was used to analyze the interaction between KLF13 and PGC-1α. Results indicated that KLF13 was highly expressed in LPS-treated A549 cells. KLF13 upregulation elevated the viability and reduced the levels of inflammatory factors in A549 cells exposed to LPS. Moreover, KLF13 gain-of-function inhibited LPS-induced apoptosis of A549 cells, accompanied by upregulated BCL2 expression and downregulated Bax and cleaved caspase3 expression. Furthermore, MQC was improved by KLF13 overexpression, as evidenced by decreased MitoSOX, JC-1 monomers and increased JC-1 aggregates, coupled with the changes of proteins related to MQC. In addition, Co-IP assay confirmed the interaction between KLF13 and PGC-1α. PGC-1α deficiency restored the impacts of KLF13 upregulation on the inflammation, apoptosis, and MQC in LPS-treated A549 cells. In conclusion, KLF13 attenuated LPS-induced alveolar epithelial cell inflammation and apoptosis by regulating MQC via binding PGC-1α.</p>","PeriodicalId":16261,"journal":{"name":"Journal of Interferon and Cytokine Research","volume":null,"pages":null},"PeriodicalIF":1.9,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141476790","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Psoriasis is a chronic, immune-mediated inflammatory skin disease characterized by epidermal thickening and inflammatory cell infiltration. Excessive proliferation of keratinocytes and resistance to apoptosis lead to thickening of the epidermis. Plasmacytoid dendritic cells are involved in the occurrence of psoriasis mainly by secreting interferon-alpha (IFN-α). IFN-α is a glycoprotein with antiviral, antitumor, and immunomodulatory effects, but its role in psoriasis remains unclear. In this investigation, a mild psoriatic phenotype was observed in mice upon topical application of IFN-α cream, and the inflammation was exacerbated when combined with imiquimod (IMQ). Immunohistochemical analyses demonstrated that IFN-α induces psoriatic inflammation in mice by stimulating phosphorylation of forkhead box O3, consistent with the involvement of this protein in cell proliferation, apoptosis, and inflammation. Our results suggested that topical IFN-α caused psoriatic inflammation and that the psoriatic inflammation was exacerbated by the combination of IFN-α and IMQ, possibly due to the dysfunction of forkhead box O3.
{"title":"Interferon-Alpha Induces Psoriatic Inflammation in Mice by Phosphorylating FOXO3.","authors":"Hanjiang Gu, Xiaoyu Wang, Mei Lu, Yaqi Wang, Kaixuan Ren, Yitian Zhang, Wei Liu, Guanglei Hu, Weihui Zeng, Yumin Xia","doi":"10.1089/jir.2023.0225","DOIUrl":"10.1089/jir.2023.0225","url":null,"abstract":"<p><p>Psoriasis is a chronic, immune-mediated inflammatory skin disease characterized by epidermal thickening and inflammatory cell infiltration. Excessive proliferation of keratinocytes and resistance to apoptosis lead to thickening of the epidermis. Plasmacytoid dendritic cells are involved in the occurrence of psoriasis mainly by secreting interferon-alpha (IFN-α). IFN-α is a glycoprotein with antiviral, antitumor, and immunomodulatory effects, but its role in psoriasis remains unclear. In this investigation, a mild psoriatic phenotype was observed in mice upon topical application of IFN-α cream, and the inflammation was exacerbated when combined with imiquimod (IMQ). Immunohistochemical analyses demonstrated that IFN-α induces psoriatic inflammation in mice by stimulating phosphorylation of forkhead box O3, consistent with the involvement of this protein in cell proliferation, apoptosis, and inflammation. Our results suggested that topical IFN-α caused psoriatic inflammation and that the psoriatic inflammation was exacerbated by the combination of IFN-α and IMQ, possibly due to the dysfunction of forkhead box O3.</p>","PeriodicalId":16261,"journal":{"name":"Journal of Interferon and Cytokine Research","volume":null,"pages":null},"PeriodicalIF":1.9,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140335913","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-01Epub Date: 2024-04-12DOI: 10.1089/jir.2024.0030
Harshika Khanna, Sarika Gupta, Yasmeen Sheikh
Cell-mediated immune response is critical for Mycobacterium tuberculosis (M.tb) control. Understanding of pathophysiology and role played by different cell mediators is essential for vaccine development and better management of patients with M.tb. A complex array of cytokines and chemokines are involved in the immune response against M.tb; however, their relative contribution in protection remains to be further explored. The purpose of this review is to summarize the current understanding regarding the cytokine and chemokine profiles in M.tb infection in order to assist research in the field to pursue new direction in prevention and control. We have also summarized recent findings on vaccine trials that have been developed and or are under trials that are targeting these molecules.
{"title":"Cell-Mediated Immune Response Against <i>Mycobacterium tuberculosis</i> and Its Potential Therapeutic Impact.","authors":"Harshika Khanna, Sarika Gupta, Yasmeen Sheikh","doi":"10.1089/jir.2024.0030","DOIUrl":"10.1089/jir.2024.0030","url":null,"abstract":"<p><p>Cell-mediated immune response is critical for <i>Mycobacterium tuberculosis</i> (<i>M.tb</i>) control. Understanding of pathophysiology and role played by different cell mediators is essential for vaccine development and better management of patients with <i>M.tb</i>. A complex array of cytokines and chemokines are involved in the immune response against <i>M.tb</i>; however, their relative contribution in protection remains to be further explored. The purpose of this review is to summarize the current understanding regarding the cytokine and chemokine profiles in <i>M.tb</i> infection in order to assist research in the field to pursue new direction in prevention and control. We have also summarized recent findings on vaccine trials that have been developed and or are under trials that are targeting these molecules.</p>","PeriodicalId":16261,"journal":{"name":"Journal of Interferon and Cytokine Research","volume":null,"pages":null},"PeriodicalIF":1.9,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140859384","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}