Central European Journal of Immunology最新文献

Introduction: Toll-like receptors (TLRs) contribute to the innate immune system. They are an element of non-specific immunity, which enables organisms to react quickly to foreign antigens, without being previously exposed to them. TLRs are pattern recognition receptors. TLR gene polymorphisms are widely investigated in connection with various infections. The aims of the study were: to investigate the role of TLR2 and TLR4 polymorphisms in the course of urinary tract infections (UTIs); to test for differences in distribution of these polymorphisms between children with urinary tract malformations suffering from recurrent UTI (rUTI), children with malformations but without rUTI and healthy controls; to determine whether these polymorphisms predispose to rUTI; and to analyse how polymorphisms and urine neutrophil gelatinase-associated lipocalin (NGAL) and interleukin 8 (IL-8) concentrations affect one another.

Material and methods: The group consisted of 133 children (1-18 years old), 68 female and 65 male. The group was divided into 4 subgroups: A (rUTI with urinary tract malformations), B (urinary tract malformations without rUTI), C (rUTI) and D (healthy controls). Polymorphisms were analysed using PCR-RFLP. IL-8 and NGAL urine concentrations were established using immunoenzymatic methods.

Results: TLR2 Arg753Gln and TLR4 Arg299Gly appeared significantly more often among children with rUTI. No correlation between urine IL-8 and urine NGAL and polymorphisms was found. Urine NGAL concentration was significantly higher among children with urinary tract malformations.

Conclusions: TLR2 Arg753Gln and TLR4 Asp299Gly may predispose to rUTI. Urine NGAL concentration suggests the presence of kidney tissue injury, of varying degrees, among children with urinary tract malformations.

Interleukin 25 (IL-25), also known as IL-17E, is a member of the IL-17 cytokine family and an important regulator of the type 2 immune response. Accumulating evidence suggests that IL-25 interacts with diverse immune as well as non-immune cells and plays a rather complicated role in different backgrounds of multiple organs. IL-25 has been studied in the physiology and pathology of the intestine to some extent. With epithelial cells being an important source in the intestine, IL-25 plays a key role in intestinal immune responses and is associated with inappropriate allergic reactions, autoimmune diseases, and cancer tumorigenesis. In this review, we discuss the emerging comprehension of the biology of IL-25, as well as its cellular sources, targets, and signaling transduction. In particular, we discuss how IL-25 participates in the development of intestinal diseases including helminth infection, inflammatory bowel diseases, food allergy and colorectal cancer, as well as its underlying role in future therapy.

Introduction: Breast cancer (BC) is associated with an inflammatory microenvironment. In BC, epidemiological evidence suggests that inflammation is associated with a poor prognosis. However, approaches to determine the extent of inflammation in the tumor microenvironment remain unclear.

Material and methods: We downloaded the expression profiles and corresponding clinicopathological information of 1050 BC tissues and 59 cases of normal breast tissue from The Cancer Genome Atlas (TCGA) dataset. Similarly, data of 1050 BC tissues were downloaded from Gene Expression Omnibus (GEO) and 200 inflammation-related genes were downloaded from the MSigDB database. We developed an inflammatory risk model to reflect the immune microenvironment in BC.

Results: Multivariate Cox analysis showed that the risk score was an independent predictor of overall survival (OS). Inflammatory signature was significantly associated with clinical and molecular features and could serve as an independent prognostic factor for BC patients. Furthermore, most immune cells were significantly less infiltrated in the high-risk group than in the low-risk group. There was a significant difference in survival time between the group with a high and low tumor mutational burden (TMB) score, and the survival time of the patients with a low TMB was significantly higher than that of the high-risk group. The risk scores were significantly lower in patients who responded to immunotherapy (complete response/partial response - CR/PR) than in patients who did not respond to immunotherapy (stable disease/progressive disease - SD/PD).

Conclusions: We developed and validated an inflammatory risk model, which served as an independent prognostic indicator and reflected immune response intensity in the BC microenvironment.

Predicting which patients will need the intensive care unit (ICU) due to severe COVID-19 is critical in terms of disease treatment. In this study, the use of the derived isohemagglutinin (dIH) parameter calculated from isohemagglutinin (IH) values and neutrophil to lymphocyte ratios for prediction of clinical care (CLC), ICU admission and mortality status was investigated for the morbidity and mortality of COVID-19. The data of approximately 21,500 patients admitted to the hospital with the suspicion of COVID-19 were scanned retrospectively. A total of 352 patients with IH results were divided into three groups according to CLC, ICU admission and mortality. Isohemagglutinin, hemogram and biochemistry test results, demographic characteristics, chronic diseases, length of stay, treatments, ICU admission and mortality records were reviewed for all patients. The relationship between test results, demographic characteristics, clinical status and mortality was investigated using statistical methods. The dIH values of patients with ICU admission and mortality were much lower than those of CLC patients [median (min-max): 3.34 (0.14-95.8) and 0.82 (0.05-42.3) vs. 0.18 (0.01-20.6) titers, p < 0.01, respectively]. In the ROC analysis for the power of dIH to discriminate ICU admission, the cutoff was ≤ 0.68 with sensitivity 88.9%, and specificity 79.6%. It was determined that a 1-unit increase in dIH values decreased the need for ICU by 2.09 times and the mortality of those receiving ICU treatment by 2.02 times. dIH values calculated in the early stages of the disease in patients with COVID-19 can be used to estimate the clinical progression associated with ICU admission and mortality.

Introduction: Adult and pediatric data suggest a positive relationship between the extent of subclinical inflammation, blood pressure, and hypertension-mediated organ damage (HMOD) in primary hypertension (PH). 24-hour (24-h) ambulatory blood pressure (ABPM) and central blood pressure (CBP) are strong predictors of HMOD. Our study aimed to analyze the relationship between 24-h central ABPM, subclinical inflammation, and clinical data in adolescents with PH.

Material and methods: In 28 untreated adolescents with PH (14.50 ±2.27 years) and 25 healthy peers (14.76 ±2.83 years), we analyzed 24-h peripheral and central ABPM, markers of subclinical inflammation (neutrophil-to-lymphocyte ratio - NLR, platelet-to-lymphocyte ratio - PLR, mean platelet volume - MPV), and clinical and biochemical data.

Results: Patients with PH had higher 24-h peripheral and central blood pressure than healthy peers. In all 53 patients, we found significant (p < 0.05) positive correlations between NLR, PLR and 24-h central systolic, diastolic, and mean blood pressure (24-h cSBP, 24-h cDBP, 24-h cMAP), between 24-h central augmentation index corrected for heart rate 75 (24-h cAIx75HR) and platelet count. In 28 patients with PH, 24-h cAIx75HR correlated with low-density lipoprotein (LDL) cholesterol (R = 0.442), and ambulatory arterial stiffness index with body mass index (BMI) (R = 0.487), uric acid (R = 0.430), and high-density lipoprotein (HDL) cholesterol (R = -0.428).

Conclusions: Increased central 24-h blood pressure may be associated with immune system activation in adolescents with primary hypertension. In adolescents with primary hypertension, dyslipidemia and hyperuricemia are risk factors for increased arterial stiffness. Further studies on central and peripheral blood pressure in terms of their relationship with inflammation in these patients are needed.

The main function of the immune system is to protect against infectious pathogens and to ensure tissue homeostasis. The latter function includes preventing autoimmune reactions, tolerizing cells to nonpathogenic environmental microorganisms, and eliminating apoptotic/damaged, transformed, or neoplastic cells. The process of carcinogenesis and tumor development and the role of the immune system in inhibiting progression of cancer have been the subject of intense research since the end of the 20^th century and resulted in formulation of the cancer immunoediting hypothesis. The hypothesis postulates three steps in oncogenesis: 1) elimination - corresponding to immunosurveillance, 2) equilibrium in which the growth of transformed or neoplastic cells is efficiently controlled by immune effector mechanisms, and 3) escape in which cancer progresses due to an ineffective antitumor response. In parallel, a new field of science - immune-oncology - has arisen. Attempts are also being made to quantify intra-tumoral and peritumoral T cell infiltrations and to define optimal immunological parameters for prognostic/predictive purposes in several types of cancer. The knowledge of relationships between the tumor and the immune system has been and is practically exploited therapeutically in the clinic to treat cancer. Immunotherapy is a standard or supplementary treatment in various types of cancer.

Atherosclerosis (AS) has been reported to induce severe clinical complications. Circular RNA (circRNA) circ_0090231 was found to be aberrantly overexpressed in oxidized low-density lipoprotein (ox-LDL)-induced endothelial cells. This study was designed to explore the role and mechanism of circ_0090231 in ox-LDL-triggered endothelial cell injury in AS. Circ_0090231, microRNA-9-5p (miR-9-5p), and thioredoxin interacting protein (TXNIP) levels were detected by real-time quantitative polymerase chain reaction (RT-qPCR). Cell viability, angiogenesis, and apoptosis were detected by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT), tube formation, and flow cytometry assay. Bcl-2, Bax, and TXNIP protein levels were gauged by western blot assay. Malondialdehyde (MDA), lactate dehydrogenase (LDH), and superoxide dismutase (SOD) activity were determined by special kits. Tumor necrosis factor α (TNF-α), interleukin-1β (IL-1β), and interleukin 6 (IL-6) levels were analyzed using enzyme-linked immunosorbent assay (ELISA) kits. The binding relationship between miR-9-5p and circ_0090231 or TXNIP was predicted by starBase, and then verified by a dual-luciferase reporter and RNA immunoprecipitation (RIP) assays. Circ_0090231 and TXNIP were increased, and miR-9-5p was decreased in ox-LDL-treated HUVECs. Moreover, circ_0090231 knockdown mitigated ox-LDL-induced HUVEC injury by boosting angiogenesis, oxidative stress, and inflammation, and hindering apoptosis. The mechanical analysis revealed that circ_0090231 acted as a sponge of miR-9-5p to regulate TXNIP expression. Circ_0090231 could attenuate ox-LDL-mediated HUVEC damage by the miR-9-5p/TXNIP axis, providing a promising therapeutic strategy for AS treatment.

Congenital obstructive nephropathy (CON) is one of the most common causes of chronic kidney disease in children. The aim of the study was to investigate serum and urine periostin and cytokeratin-18 (CK-18) in children with CON in relation to CON etiology, treatment, and kidney injury. We evaluated 81 children with CON secondary to ureteropelvic junction obstruction (UPJO), ureterovesical junction obstruction (UVJO), posterior urethral valves (PUV) and 60 controls. Neither biomarker demonstrated any relation to CON etiology. However, all patients showed significantly higher urine periostin (uPeriostin) and uPeriostin/Cr levels than the controls. Also, UVJO patients showed higher sCK-18 and uCK-18/Cr levels, and PUV patients showed higher uCK-18/Cr levels than the controls. Neither biomarker was found to have any relation to CON treatment. However, conservatively treated children and those before and after surgery showed significantly higher uPeriostin and uPeriostin/Cr levels than the controls. uPeriostin strongly correlated with differential renal function (DRF) < 40%. The ROC analysis demonstrated the best area under the curve (AUC) for uPeriostin (0.831) and uPeriostin/Cr (0.768), and low for sPeriostin (0.656) and uCK-18 (0.615) for detecting renal injury. In conclusion, although serum and urine periostin and CK-18 did not display any relation to etiology or the type of CON treatment, uPeriostin seems to be a useful tool for detecting renal injury in children with CON, especially due to its strong negative correlation with DRF < 40%.

Chronic inflammation develops when the immune system is unable to clear a persistent insult. Unresolved chronic inflammation leads to immunosuppression to maintain the internal homeostatic conditions, which is mediated primarily by myeloid-derived suppressor cells (MDSCs). Toll-like receptors 2 (TLR2) has an important role in chronic inflammation and can be activated by a vast number and diversity of TLR2 ligands, for example Pam2CSK4. However, the regulatory effect of TLR2 signaling on MDSCs in chronic inflammation remains controversial. This study demonstrated that heat-killed Mycobacterium bovis BCG-induced pathology-free chronic inflammation triggered suppressive monocytic MDSCs (M-MDSCs) that expressed TLR2. Activation of TLR2 signaling by Pam2CSK4 treatment enhanced immunosuppression of M-MDSCs by upregulating inducible nitric oxide synthase (iNOS) activity and nitric oxide (NO) production partly through signal transducer and activator of transcription 3 (STAT3) activation. Thus, TLR2 has a fundamental role in promoting the MDSC-mediated immunosuppressive environment during chronic inflammation and might represent a potentially therapeutic target in chronic inflammation disease.