IL-17F Gene Research Articles

The role of IL-23/IL-17 axis in human kidney allograft rejection.

Th17 cell subset has been implicated in autoimmune diseases, tumor immunity and, transplant rejection. In order to investigate the role of IL-17/IL-23 pathway in allograft outcome, intragraft expression of IL-17mRNA and single nucleotide polymorphisms (SNPs) of IL-17A, IL-17F, IL-17RC, and IL23R genes were evaluated with a quantification of IL-17A, IL-17F, and IL-23 plasma levels. This study revealed that recipients with acute rejection (AR) had a significant increase in IL-17AmRNA expression levels after transplantation compared to controls (P=0.037). Moreover, IL-17A plasma levels were significantly higher in AR group; pretransplantation (Day-1 [D-1]): P=0.00022 and posttransplantation (Day 7 [D7]): P<10-14 . IL-17F and IL-23 plasma levels were significantly higher in AR at D7 only (47.86vs. 22.99pg/ml; and 33.82vs. 18.811pg/ml; P=0.015 and P<10-17 , respectively). Using receiver-operating characteristic curves, D7 IL-17A and IL-23 plasma levels exhibited excellent sensitivities and specificities for predicting AR. Genetic study revealed no association between IL-17A, IL-17F, IL-17RC, and IL23R studied SNPs and AR. Nevertheless, a significant improvement of graft survival was found in kidney transplant recipients carrying IL-17F-rs763780*A/A, IL-17RC*G/G, and *G/A genotypes. Besides, IL-17AmRNA levels were significantly higher in patients carrying the IL-23R*G/G genotype comparatively to those with *G/A genotype. Based on these findings, significant increase of IL-17A mRNA and protein levels in AR recipients that are genetically controlled highlights the role of this cytokine that can be a useful clinical biomarker to predict early acute renal allograft rejection.

Involvement of the IL23/Th17 Pathway in the Pathogenesis of Tunisian Pemphigus Foliaceus.

Pemphigus foliaceus (PF) is a rare autoimmune skin disease caused by anti-Dsg1 pathogenic autoantibodies. It is considered as a Th2-mediated disease. Likewise, Th17 cells were recently described in the pathogenesis of the disease but their role is still unclear. We aimed to unravel the eventual implication of the IL23/Th17 pathway in the development of PF. A case-control study was conducted on 115 PF patients and 201 healthy controls using PCR-RFLP and AS-PCR methods. SNPs in IL23R, RORγt, IL17A, IL17F, IL17AR, TNFa, and STAT3 genes were genotyped. mRNA expression of IL23R and RORγt was evaluated using Q-PCR. The frequency of circulating Th17 cells was analyzed by flow cytometry. Genetic associations between IL23R>rs11209026, IL17A>rs3748067, IL17F>rs763780, and TNFa>rs1800629 and the susceptibility to PF were reported. Moreover, we revealed a significant increased frequency of circulating CD4+IL17+ cells as well as higher mRNA levels of RORγt and IL23R in PBMCs of patients. However, no significant increase of RORγt and IL23R mRNA expression was observed in lesional skin biopsies. In spite of the little size of specimens, our results provide converging arguments for the contribution of the IL23/Th17 pathway in the pathogenesis of PF.

Association of IL17 and IL23R gene polymorphisms with rheumatic heart disease in South Indian population

ABSTRACTBackground: IL-23/Th17 signaling pathway plays a crucial role in the cell-mediated immune response against bacterial infections and also in the pathogenesis of inflammatory and autoimmune diseases. Recent studies indicate that Th17 cell-associated cytokines are involved in the progression and maintenance of valvular lesions in rheumatic heart disease (RHD). Variants in the genes of cytokines that are potentially involved in Th17 response may influence interindividual differences in their expression levels, thereby contributing to the pathogenesis of immune-mediated diseases such as RHD.Objective: The aim of the study is to investigate the association of IL17A, IL17F, and IL23R gene variants with the risk perception of RHD.Methods: A total of 225 individuals (99 RHD patients and 126 healthy siblings) were recruited for the study. The IL17A (rs2275913), IL17F (rs763780), and IL23R (rs10889677) polymorphisms were determined by polymerase chain reaction restriction fragment length polymorphisms and amplification-refractory mutation system-polymerase chain reaction methods, respectively.Results: The frequency of IL17A (rs2275913) A/A genotype was significantly high in pooled RHD patients (odds ratio [OR] = 2.76; pc = 0.021), rheumatic fever (RF) patients (OR = 14.5; pc = 0.0001), and mitral valvular lesions patients (OR = 2.74; pc = 0.039) when compared to healthy siblings. However, the IL17F (rs763780) and IL23R (rs10889677) polymorphisms did not show any association with RHD.Conclusions: The results suggest that IL17A (rs2275913) polymorphism is associated with the development of RF/RHD in South Indian population. Further studies are required to substantiate the association of these genes with the disease risk.

IL-17A gene polymorphism at position G197A and systemic lupus erythematosus

Systemic lupus erythematosus (SLE) is a multi-systemic disorder with various clinical manifestations. Lupus is a multifactorial autoimmune disease resulting from complex gene-environment interactions. IL-17 is a pro-inflammatory cytokine secreted by Th-17 cells, and IL-17A and IL-17F are two predominant members of this family. The present study assessed the association of IL-17F (rs763780) gene polymorphism with SLE. A total of 102 SLE patients and 141 healthy subjects were enrolled in this case-control study. Genotyping was done using the PCR-RFLP technique. The results were analyzed using SPSS software. Results showed a borderline relationship between the heterozygote genotype (AG) and a reduced risk of SLE (OR: 0.31, 95% CI: 0.09-1.0, P=0.05). The A allele was also shown as having a protective effect on SLE susceptibility (OR: 0.68, 95% CI: 0.46-1.0, P=0.05). No association was observed between the genotypes of the IL-17F gene polymorphism and the risk of SLE (P>0.05). In conclusion, it seems that the IL-17A gene may be involved in the pathogenesis of SLE.

Genetic polymorphisms of IL-17A rs2275913, rs3748067 and IL-17F rs763780 in gastric cancer risk: evidence from 8124 cases and 9873 controls.

Interleukin-17 (IL-17) is a critical cytokine involved in inflammation-associated cancers. Single nucleotide polymorphisms (SNPs) might promote carcinogenesis. In this current meta-analysis, we investigated the association of IL-17A and IL-17F gene polymorphisms with gastric cancer (GC) risk. Eligible genetic association studies were retrieved from PubMed, Web of Science and Scopus database sources. Two reviewers independently assessed methodological quality and extracted data from eligible articles. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. Quantitative data synthesis was conducted using comprehensive meta-analysis v2. Subgroup analysis and heterogeneity analysis were performed. Begg's funnel plot and Egger's regression tests were used to judge publication bias. In silico data analysis was executed to analyze the functional and structural impact of the SNPs. A total of 21 case-control studies for rs2275913 c.-197G > A (7660 patients and 9409 controls), 9 studies for rs3748067 c.*1249C > T (3378 patients and 4120 controls), and 14 studies for rs763780 c.482A > G (4481 patients and 5354 controls) were included. The pooled estimate revealed an association between IL-17A rs2275913 polymorphism and the risk of GC under all genetic models (A vs. G, OR 1.187, 95% CI 1.086-1.297, P < 0.001; GA vs. GG, OR 1.108, 95% CI 1.008-1.218, P = 0.033; AA vs. GG, OR 1.484, 95% CI 1.236-1.781, P < 0.001), while no evidence of association was found with IL-17A rs3748067 or IL-17F rs763780 polymorphisms. Our results showed that IL-17A promoter rs2275913 variant might represent a potential risk factor for gastric cancer susceptibility.

Association between interleukin-17 gene polymorphism and rheumatoid arthritis among Egyptians

BackgroundRheumatoid arthritis (RA) is an autoimmune systemic inflammatory disorder characterized by synovial inflammation, destruction of joints and systemic manifestations. Interleukin-17 (IL-17) is a pro-inflammatory cytokine that plays an important role in the pathogenesis of RA. ObjectiveThis study aimed to examine the associations between both IL-17A (197A/G; rs2275913) and IL-17F (7488A/G; rs763780 and 7383 A/G; rs2397084) gene polymorphisms and the susceptibility of RA among Egyptian population. MethodsIL-17A and IL-17F gene polymorphisms were determined in ninety eight patients with RA and ninety five healthy control subjects using polymerase chain reaction based restriction fragment length polymorphism (RFLP) analysis. ResultsThere was no significant difference in the genotype and allele frequencies of IL-17A (rs2275913) and IL-17F (rs763780 and rs2397084) between the controls and the patients with RA (P > 0.05). ConclusionThe results of this study suggested that the IL-17A and IL-17F gene polymorphisms may not be associated with the susceptibility to RA among Egyptian population.

Study of the role of IL-17F gene polymorphism in the development of immune thrombocytopenia among the Egyptian children

BackgroundInterleukin 17F (IL-17F) is a pro-inflammatory cytokine that is recently proved to have a crucial role in the emergence of autoimmune diseases; it induces the expression of various cytokines, chemokines, and adhesion molecules. IL-17F polymorphism is subsequently related to enhanced IL-17F expression and activity; which may result in susceptibility to many autoimmune diseases including primary immune thrombocytopenia (PIT). Aim of the studyThis case-control study aimed to investigate the possible association between IL and 17F gene single nucleotide polymorphism (SNP) at rs 7488A/G and PIT susceptibility in Egyptian pediatric patients. Subjects and methodsA total of 50 children with PIT with a mean age of 7 years, together with 50 age and sexmatched healthy controls were enrolled in the study for evaluation. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used for detection of IL-17F polymorphism at rs7488A/G. ResultsRegarding the genotypes distribution, the frequencies of the AA, AG and GG genotypes were 96, 2, and 2% in PIT patients and 90, 10 and 0% in the control group respectively. The A and G allele frequencies were 97 and 3% in the patients’ group versus 95 and 5% in the control group. There was no significant difference in either genotypes or allelic distribution between PIT patients and the controls. ConclusionOur study suggests that IL17F gene polymorphism at rs7488A/G may not contribute to the susceptibility in development of primary immune thrombocytopenia in the Egyptian children.

IL1F7 Gene Polymorphism Is not Associated with Rheumatoid Arthritis Susceptibility in the Northern Chinese Han Population: A Case-Control Study.

Background:Interleukin (IL)-37, also called IL1F7, is a natural inhibitor of inflammatory and immune responses. It is involved in the pathogenesis of rheumatoid arthritis (RA). This study aimed to investigate the role of IL1F7 gene polymorphism in RA susceptibility in a large cohort of patients.Methods:Five selected single-nucleotide polymorphisms in IL1F7 genes (rs2723186, rs3811046, rs4241122, rs4364030, and rs4392270) were genotyped by TaqMan Allelic Discrimination in Northern Chinese Han population. The allele and the genotype were compared between patients with RA and healthy controls. Association analyses were performed on the entire data set and on different RA subsets based on the status of the anti-cyclic citrullinated peptide antibody and the rheumatoid factor by logistic regression, adjusting for age and gender.Results:Trend associations were detected between rs2723186, rs4241122, rs4392270, and RA in Stage I (160 patients with RA; 252 healthy controls). Further validation in Stage II comprised 730 unrelated patients with RA (mean age: 54.9 ± 12.6 years; 81.6% females) and 778 unrelated healthy individuals (mean age: 53.5 ± 15.7 years; 79.5% females). No significant differences in the distributions of alleles and genotypes were observed between the case and control groups in both the entire set and the different RA subsets. Disease activity and age of RA onset were also not associated with genotype distributions.Conclusion:IL1F7 gene polymorphism does not significantly influence RA susceptibility in the Northern Chinese Han population.

Association of genetic polymorphism of interleukin-17A & interleukin-17F with susceptibility of psoriasis.

Background & objectives:Psoriasis is a chronic inflammatory skin disease with unknown aetiology. So far studies have confirmed that interleukins, pro-inflammatory factors and T-cell activation play major role in the development of disease. Interleukin-17 (IL-17) a T helper inflammatory cytokine, was found to be positively correlated with severity of psoriasis. However, the specific mechanism has not been clarified. IL-17A and IL-17F are group members of IL17 family cytokines and found to be located adjacent to one another on the same human chromosome, 6p12. The present study was designed to identify the association between IL-17A and IL-17F gene polymorphism with susceptibility of psoriasis in north Indian population.Methods:A total of 166 psoriasis patients and 150 healthy controls were genotyped for IL-17A and IL-17F gene polymorphism by amplification refractory mutation system-polymerase chain reaction method. One single nucleotide polymorphism (SNP) was analysed in IL-17A (rs10484879) and one SNP in IL-17F (rs763780) to look for an association with psoriasis.Results:Our study indicated decreased frequency of IL-17A (rs10484879) G allele (51.8 vs. 65.0%), and IL-17F (rs763780) C allele (36.5 vs. 45.7%) in psoriatic patients as compared to healthy controls.Interpretation & conclusions:The present findings suggest that IL-17A (rs10484879) G/T and IL-17F (rs763780) C/T gene polymorphisms may contribute in pathogenesis of psoriasis. Further studies need to be done to confirm these findings.

Impact of Interleukin-17F Gene Polymorphisms in Outcome of Kidney Transplantation in Tunisian Recipients

BackgroundGenetic polymorphisms of interleukin (IL)-17F, associated with functional and/or quantitative change in this glycoprotein, have been described as predisposing to various autoimmune diseases. The proinflammatory IL-17 has some roles in renal transplantation. In this context, the relationship between the most common IL-17F polymorphisms with acute renal allograft rejection susceptibility in Tunisian renal recipients has been investigated. MethodsWe examined 93 renal transplant recipients who were enrolled and classified as follows: GI, 48 transplant recipients who developed at least one episode of acute rejection; and GII, 45 controls, kidney recipients who also were followed for at least 1 year and had stable renal function. Single nucleotide polymorphisms (SNPs) of IL-17F gene, including -1507 C/T (rs18889570), 7384 A/G (rs2397084), 7469 C/T (rs11465553), and 7489 A/G (rs763780), were evaluated using direct sequencing. ResultsNo statistically significant association of the IL-17F SNPs studied with the onset of acute rejection was observed. However, AA genotype on 7489A/G SNP showed anti-HLA antibodies less than other genotypes and a higher graft survival time (P = .017). ConclusionThe AA genotype on 7489A/G SNP of IL-17F and the A allele might be associated with a lower risk of acute rejection with better graft survival.

Association of IL-17A and IL-17F Gene Polymorphisms with Acute Immune Thrombocytopenia in Egyptian Children

Background: IL-17 is an inflammatory cytokine that plays a crucial role in many autoimmune diseases. Aim: To investigate the association of IL-17A rs2275913 and IL-17F rs763780 gene polymorphisms with acute immune thrombocytopenic purpura (ITP) in Egyptian children. Patients and methods: We examined 80 patients (male/female, 33/47; median age, 7 years old) diagnosed with acute ITP and 55 healthy controls (male/female, 28/27; median age, 7 years old). Genotyping was determined using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. Results: In the acute ITP group compared to control, statistical analysis of the genotype frequencies (GG, AG, AA) of the IL-17A rs2275913 polymorphism and its alleles (A, G) showed no significant difference between the two groups (p > 0.05). Interestingly, the IL17A rs2275913 GG genotype was associated with early recovery (p = 0.04). As regard the genotype frequencies of the IL-17F rs763780 polymorphism, there was statistical significant difference in the TT and TC genotype frequencies between the case and control groups (p = 0.001 and p = 0.003, respectively). The number of IL-17F rs763780 T alleles was significantly higher in acute ITP patients as compared with children in the control group (p Conclusion: The present findings indicate that the IL-17 polymorphism IL-17F rs763780, but not IL-17A rs2275913 may be associated with a higher risk of acute ITP in Egyptian children.

Oral Administration of Vanillin Improves Imiquimod-Induced Psoriatic Skin Inflammation in Mice.

Vanillin is one of the most widely used flavoring products worldwide. Psoriasis is a chronic inflammatory skin disorder. The interleukin-23 (IL-23)/interleukin-17 (IL-17) axis plays a critical role in psoriasis. Here, we analyzed the effect of vanillin on imiquimod (IMQ)-induced psoriatic skin inflammation in mice. Mice were treated topically with IMQ on the back skin and orally with various amounts of vanillin for 7 consecutive days. Vanillin significantly improved IMQ-induced histopathological changes of skin in a dose-dependent manner. The thickness and number of cell layers of epidermis were reduced by 29 ± 14.4 and 27.8 ± 11%, respectively, in mice given 100 mg/kg of vanillin. A microarray showed that a total of 9042 IMQ-upregulated genes were downregulated by vanillin, and the biological pathways involved in the immune system and metabolism were significantly altered by vanillin. The upregulated expressions of IL-23, IL-17A, and IL-17F genes were suppressed by vanillin, with fold changes of -3.07 ± 0.08, -2.06 ± 0.21, and -1.62 ± 0.21, respectively. Moreover, vanillin significantly decreased both the amounts of IL-17A and IL-23 and the infiltration of immune cells in the skin tissues of IMQ-treated mice. In conclusion, our findings suggested that vanillin was an effective bioactive compound against psoriatic skin inflammation. Moreover, the downregulation of IL-23 and IL-17 expression suggested that vanillin was a novel regulator of the IL-23/IL-17 axis.

Genetic variants of immune-related genes IL17F and IL10 are associated with functional dyspepsia: A case-control study.

Low-grade inflammation may play an important role in pathogenesis of functional dyspepsia (FD). Since cytokines may influence gastric mucosal inflammation, which is associated with FD, we evaluated singe nucleotide polymorphisms (SNPs) of pro-inflammatory IL17F and anti-inflammatory IL10 cytokine genes in patients with FD and healthy subjects (HS). Two hundred and thirty-seven consecutive patients with FD (Rome III) and 250 HS were genotyped for IL17F (rs2397084: A/G, rs763780: T/C) and IL10 (rs1800896: G/A, rs1800871: C/T) (PCR-RFLP). Patients with FD [173 (73%) men, age 38.4±12years] were comparable with HS [195 (78%) men, age 37.3±12years] with respect to age and gender. Out of 237 patients, 26 (11%) had epigastric pain, 55 (23.2%) had post-prandial distress syndromes (EPS, PDS), and 156 (65.8%) had EPS-PDS overlap. Among 237 patients with FD, GG (variant) genotype of IL17F (rs2397084) was more common than HS [15 (6.3%) vs. 4 (1.6%), p=0.015, odds ratio (OR)=4.0, 95% confidence interval (CI)=1.3-12.3]. IL17F (rs763780) and IL10 (rs1800896) were comparable among patients and HS (p=0.56, 0.28), respectively. However, TT (variant) genotype of IL10 (rs1800871) was more common among patients than HS [39 (16.5%) vs. 32 (12.8%), p=0.06, OR=1.7, 95% CI=0.98-2.98]. SNPs of IL17F and IL10 (rs2397084, rs763780, rs1800896 and rs1800871) were comparable among patients among sub-types of FD (p=0.80 and 0.44). SNPs of IL17F (rs2397084) and IL10 (rs1800871) genes are associated with FD.

Is rs763780 in IL-17F gene considered risk factor to multiple sclerosis in Egyptian patients?

Despite major efforts by the scientific community over the years, our understanding of the pathogenesis or the mechanisms of injury of multiple sclerosis is still limited. Multiple lines of evidence implicate that T cells play a central role in both mediating and regulating MS pathophysiology, and efforts to develop rational therapeutic strategies for MS have focused on understanding factors which control T cell function. So, aim of this study is to determine the association between the polymorphic features located within the IL-17F gene and susceptibility to MS in Egyptian patients. In this study, single nucleotide polymorphism (SNP) (rs763780; T7488C; His161Arg) of IL-17 F gene was genotyped in 178 Egyptians divided into 83 MS patients and 95 healthy controls with matched age and sex by using Genotyping Taqman assay. All genotypic and allelic frequencies of the tested IL-17 F polymorphism were in Hardy–Weinberg equilibrium. A significantly increased frequency of rs763780 CT+CC genotypes (p=0.009, odds ratio=2.56 (95% CI: 1.4–4.7) and C allele (P=0.005, odds ratio=2.05 (95% CI: 1.24–3.39) was detected in MS patients compared to controls. Additionally, we elucidated a significantly high risk for susceptibility of the disease incidence in female cohort only (P=0.006, odds ratio=3.3 (95% CI: 1.53–7.12).IL-17 F CT genotype and C allele may be associated with a susceptibility to MS by a gender-dependent mechanism that contributes to unique predisposition in females. So this rs763780 can be considered risk factor for the development of MS in Egyptian population.

Pharmacogenetic biomarkers of response in Crohn's disease.

Crohn's disease (CD) is a chronic condition, which affects the immune system. It can also affect any part of the digestive tract and be associated with external manifestations. The causes of the disease remain unknown, although it seems to be the result of a combination of factors, such as genetic predisposition, environment, lifestyle and the composition of the microbiota, among others. The treatment protocol begins with a change in eating and smoking habits, and is continued with different lines of treatment, including corticosteroids, immunomodulators and biologic therapy (infliximab and adalimumab), which have shown differences in response among patients, especially with biologic treatment. Several studies have considered the possibility that these differences in response are caused by the genetic variability of patients. Many genes have been investigated as potential predictors of response to biological drugs, such as ADAM17, ATG16L1, EMSY, CASP9, CCNY, CNTN5, FASLG, FCGR, NOD2, PTGER4, IL13, IL1B, IL27, IL11, IL17F, TNF and TNFR genes. In this review, we will gather the information on influence of gene polymorphisms investigated to date on response to biological drugs in CD patients.

Interleukin (IL)-23 Receptor, IL-17A and IL-17F Gene Polymorphisms in Brazilian Patients with Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is a progressive, autoimmune disease for which the previous studies have shown that some functional polymorphisms can influence its etiology. Knowing this, the aim of this study was to investigate the association of +2199 A/C IL-23R (rs10889677), -197 G/A IL-17A (rs2275913), and +7488 A/G IL-17F (rs763780) gene polymorphisms with RA susceptibility and clinical features in a Brazilian population. A total of 127 RA patients and 134 healthy controls were recruited for the analyses of polymorphic variants. Genotyping was performed using RFLP-PCR. Logistic regression was used to analyze the genotype distribution of the polymorphisms. Individuals carrying the homozygous CC genotype for the IL-23R polymorphism seem to be at lower risk for RA development (OR 0.22; p=0.004), as well as those carrying the variant C allele (OR 0.56; p=0.002). For the -197 G/A IL-17A polymorphism, the wild-type genotype (GG) was significantly associated with a 3.18-fold (OR 3.18; p=0.033) increased risk for RA. In relation to the +7488 A/G IL-17F polymorphism, no significant difference was found between RA cases and control subjects (p>0.05). Moreover, when investigating the relationship between polymorphisms and clinical features, no evidence of an association was found. Our findings suggest that the variants +2199 A/C IL-23R and -197 G/A IL-17A could contribute to RA development in the studied population. However, larger studies are needed to fully understand this genetic predisposition.

The effects of direct-fed microbial supplementation, as an alternative to antibiotics, on growth performance, intestinal immune status and epithelial barrier protein expression in broiler chickens

Abstract This study was conducted to investigate the effects of Bacillus subtilis supplementation in broiler chicken diets on growth performance, feed efficiency, intestinal cytokine and tight junction (TJ) protein mRNA expression. Day-old broiler chicks (n = 140) were to one of five dietary treatments: basal diet (CON), basal diet supplemented with antibiotic (BMD) or probiotics, namely B. subtilis strain 1781 (PB1), a combination of B. subtilis strain 1104+strain 747 (PB2) or B. subtilis strain 1781+strain 747 (PB3). At 14 days of age, ileal samples were collected and used for intestinal cytokine, TJ protein and mucin gene expression analysis using qRT-PCR. The chickens fed with antibiotic (BMD) and B. subtilis strain 1781 alone (PB1) had significantly higher body weights compared to controls of the same age. Dietary supplementation with antibiotic (BMD) or probiotics (PB1, PB2, PB3) significantly improved the feed efficiency as evidenced by decreased FCR compared to controls. No differences were observed in the expression of IL1β, IL17F, IFNγ and MUC2 gene among the different treatment groups. However, elevated expression of IL6 (BMD, PB1, PB2), IL8 (PB2) and TNFSF15 (PB1, PB2, PB3) compared to controls was observed in the ileum. IL2 and IL10 expression was upregulated in chicks in the PB2 and PB3 groups, and IL4 was elevated in the PB1 group. IL13 was elevated in all probiotic-fed groups. Probiotic supplementation was also shown to significantly increase the expression of TJ proteins JAM2, ZO1 (PB2, PB3) and occludin (PB1, PB2). Taken together, B. subtilis supplementation altered intestinal immune activity and influenced gut barrier integrity through increased expression of TJ proteins.

Interleukin-17F and interleukin-6 gene polymorphisms in Asian Indian patients with Takayasu arteritis

ObjectivesTo assess genetic association between single nucleotide polymorphisms (SNPs) in genes encoding T-helper cytokines and Takayasu Arteritis (TA) susceptibility in Asian Indian population. MethodsIn Phase-1, the genomic DNA of 120 TA patients and 119 healthy controls were genotyped for SNPs rs1800795 (interleukin (IL)-6), rs763780 (IL-17F), rs1800871, rs1800872, rs1800896 (IL-10) and rs1800468, rs1800469, rs1800470 (transforming growth factor-β). Allele frequencies between cases and controls were compared using chi-squared test and also reassessed empirically (pe) by 10,000 permutations. In Phase-2, additional 98 TA patients and 101 controls were genotyped for replicating the significant associations noted in Phase-1 of the study. ResultsAll 8 SNPs in Phase 1 were in Hardy-Weinberg proportions. The G allele at rs763780 (IL-17F) was significantly associated with TA (p=0.014). We also found that rs1800795 (IL-6) was associated with tuberculosis (p=0.001) under a dominant model. In Phase-2 replication part of the study, the rs763780 showed a trend towards association with TA (p=0.08), and the magnitude and direction of the odds ratio (OR) also were consistent with results of Phase-1. In the combined analysis, protective association of the G allele of rs763780 with TA was again significant [OR (95% CI)=0.44 (0.25–0.77); p=0.0029]. The G allele was also significantly associated (p<0.05) with underlying tuberculosis (TB) and occurrence of syncope in TA. ConclusionG allele of rs763780 in IL-17F gene was protectively associated against susceptibility to TA. GG genotypes of rs1800795 in IL-6 was also associated with occurrence of tuberculosis in our patients with TA.

The Effects of Direct-fed Microbial Supplementation, as an Alternative to Antibiotics, on Growth Performance, Intestinal Immune Status, and Epithelial Barrier Gene Expression in Broiler Chickens

The objective of this study was to investigate the effects of Bacillus subtilis-based probiotic supplementation in broiler chicken diets on growth performance, feed efficiency, intestinal cytokine, and tight junction (TJ) protein mRNA expression. Zero-day-old broiler chicks (n=140) were randomly assigned to one of five dietary treatments: basal diet (CON); basal diet supplemented with either antibiotic bacitracin methylene disalicylate (BMD); or probiotics, namely, B. subtilis strain 1781 (PB1), a combination of B. subtilis strain 1104+strain 747 (PB2), or B. subtilis strain 1781+strain 747 (PB3). Body weight and feed intake were measured at 14days of age, and the feed conversion ratio (FCR) was calculated. At 14days of age, ileal samples were collected and used for intestinal cytokine, TJ protein, and mucin gene expression analysis using qRT-PCR. The chickens supplemented with antibiotic (BMD) and B. subtilis strain 1781 alone (PB1) had significantly higher body weights compared to controls of the same age. Dietary supplementation with antibiotic (BMD) or probiotics (PB1, PB2, PB3) significantly improved the feed efficiency as evidenced by decreased FCR compared to controls. No differences were observed in the expression of IL1β, IL17F, IFNγ, and MUC2 gene among the different treatment groups. However, elevated expression of IL6 (BMD, PB1, PB2), IL8 (PB2), and TNFSF15 (PB1, PB2, PB3) compared to controls was observed in the ileum. IL2 and IL10 expression was upregulated in chicks in the PB2 and PB3 groups, and IL4 was elevated in the PB1 group. IL13 was elevated in all probiotic-fed groups (PB1, PB2, PB3). Probiotic supplementation was also shown to significantly increase the expression of TJ proteins JAM2, ZO1 (PB2, PB3), and occludin (PB1, PB2). Taken together, B. subtilis supplementation altered intestinal immune activity and influenced gut barrier integrity through increased tight junction gene expression.

Cytokine gene polymorphisms in populations from Parana, Southern Brazil

In this study, were genotyped 22 single nucleotide polymorphisms (SNPs) in 13 genes that encode the pro-inflammatory (IL-1α, IL-1β, IL-1R, IL-4Rα, IL-12, IFN-γ, TNF-α, and IL-2) and anti-inflammatory (IL-1RA, TGF-β, IL-4, IL-6 and IL-10) cytokines of 350 individuals by PCR-SSP (polymerase chain reaction – sequence specific primer). A total of 473 individuals were genotyped for IL17A and IL17F genes by PCR-RFLP (restriction fragment length polymorphism). The sample consisted of healthy and unrelated subjects from a mixed population from Parana state, in the South region of Brazil. The frequency analyses and genotype data are available in the Supplementary materials and are accessible at Allele Frequency Net Database (AFND).