IL-17A/lL-17RA reduces cisplatin sensitivity of ovarian cancer SKOV3 cells by regulating autophagy / 南方医科大学学报

OBJECTIVE@#To investigate the effect of interleukin-17A (IL-17A) on chemosensitivity of ovarian cancer cells to cisplatin (DDP) and explore the mechanism in light of autophagy regulation.@*METHODS@#Ovarian cancer SKOV3 cells cultured @*RESULTS@#DDP increased the expression of IL-17RA in ovarian cancer SKOV3 cells. Treatment with IL-17A significantly reduced the susceptibility of SKOV3 cells to cisplatin-induced apoptosis (@*CONCLUSIONS@#IL-17A/IL-17RA can decrease chemosensitivity of SKOV3 cells to DDP by upregulating DDP-induced autophagy.

Effects of Jinwu Jiangu recipe on IL-17/STAT3 signals in rheumatoid arthritis synoviocytes / 中国中药杂志

This paper aimed to investigate the effects of Jinwu Jiangu recipe total extract on the IL-17/STAT3 signals in rheumatoid arthritis synovial fibroblasts(RASF). The primary RASFs were cultured by tissue piece method ， and divided into blank control group， Jinwu Jiangu recipe low dose group， Jinwu Jiangu recipe middle dose group， Jinwu Jiangu recipe high dose group， and tripterygium glycosides control group. They were then treated with corresponding serum free medium， different doses of Jinwu Jiangu recipe total extract(0.06， 0.6， 6.0 g·L⁻¹)， and tripterygium glycosides(0.03 g·L⁻¹) respectively for 24 hours. The gene expression levels of RORα， RORγt， and STAT3 mRNA were detected by polymerase chain reaction(PCR)， and the protein activity of IL-17R and pSTAT3 were measured by Western blot assay. The results showed that as compared with blank control group， the expression levels of RORα， RORγt， IL-17R and STAT3 mRNA in RASF were significantly declined(<0.01). As compared with tripterygium glycosides control group， Jinwu Jiangu recipe total extract middle dose group and high dose group can down-regulate the expression levels of RORα， RORγt， IL-17R and STAT3 mRNA(<0.05)， and the effect was more obvious in high dose group(<0.01). As compared with blank control group， the protein expression levels of IL-17R and pSTAT3 in each treatment group were obviously decreased(<0.01). As compared with tripterygium glycosides control group， Jinwu Jiangu recipe high dose group had more obvious effect in down-regulating the protein expression of pSTAT3(<0.01). Therefore， Miao medicine Jinwu Jiangu recipe total extract can down-regulate the expressions of RORα， RORγt， and STAT3 mRNA， and inhibit the protein activity of IL-17R and pSTAT3 in RASF.

Expression and clinical significance of IL-17 and IL-17 receptor in ulcerative colitis / 华中科技大学学报（医学）（英德文版）

The purpose of this study was to determine the expression levels of IL-17 in serum and IL-17 receptor (IL-17R) in intestinal mucosa tissue in patients with ulcerative colitis (UC) and controls, and evaluate their relationship with disease activity and explore the role of IL-17 in the patho-genesis of UC. A total of 36 Chinese UC patients and 60 healthy controls were enrolled in this study. Serum IL-17 and C-reactive protein (CRP) levels were determined by ELISA and immunonephelometry, respectively. The IL-17R mRNA expression levels were detected by quantitative PCR. Serum IL-17 levels were significantly elevated in UC patients as compared with those in the healthy controls (P<0.05). Among UC patients, serum IL-17 levels were significantly increased in active phase as compared with those in inactive phase (P<0.05), and correlated with CRP levels (r=0.578, P<0.01). IL-17R expression levels were higher in active UC patients than in healthy controls (P<0.05). It was concluded that IL-17 levels were highly expressed in UC, especially in active phase, and correlated with CRP levels in UC patients.

Is Whole Exome Sequencing Clinically Practical in the Management of Pediatric Crohn's Disease?

BACKGROUND/AIMS: The aim of this study was to identify the profile of rare variants associated with Crohn's disease (CD) using whole exome sequencing (WES) analysis of Korean children with CD and to evaluate whether genetic profiles could provide information during medical decision making. METHODS: DNA samples from 18 control individuals and 22 patients with infantile, very-early and early onset CD of severe phenotype were used for WES. Genes were filtered using panels of inflammatory bowel disease (IBD)-associated genes and genes of primary immunodeficiency (PID) and monogenic IBD. RESULTS: Eighty-one IBD-associated variants and 35 variants in PID genes were revealed by WES. The most frequently occurring variants were carried by nine (41%) and four (18.2%) CD probands and were ATG16L2 (rs11235604) and IL17REL (rs142430606), respectively. Twenty-four IBD-associated variants and 10 PID variants were predicted to be deleterious and were identified in the heterozygous state. However, their functions were unknown with the exception of a novel p.Q111X variant in XIAP (X chromosome) of a male proband. CONCLUSIONS: The presence of many rare variants of unknown significance limits the clinical applicability of WES for individual CD patients. However, WES in children may be beneficial for distinguishing CD secondary to PID.

Targeting Interleukin-17 and Th17 in Immune Inflammatory Diseases / 한양의대학술지

Th17 cells (Th17) are a distinct lineage of CD4+ T cells that secrete high amounts of IL-17 under orphan nuclear receptor retinoic acid receptor-related orphan receptor gammat (RORgammat) which is a lineage-specific transcription factor. TGF-beta and inflammatory cytokines, such as IL-6, IL-21, IL-1beta, and IL-23, play central roles in the generation of Th17 cells. Th17 cells and their effector molecules, such as IL-17A, IL-17F, IL-21, IL-22, and CCL20, contribute to the progression and pathogenesis of several autoimmune and inflammatory diseases, such as rheumatoid arthritis, psoriasis, multiple sclerosis, inflammatory bowel disease and systemic lupus erythematosus. Studies of Th17 development and the effects of IL-17 signaling in autoimmune responses suggest a high potential for targeting this pathway in immune pathologies. In this review, we discuss Th17 biology in relation to autoinflammatory disorders and the various therapeutic strategies under investigation which target the IL-17-Th17 cell pathway in chronic inflammatory autoimmune disorders.

Effects of interleukin-17 on murine pulmonary fibroblast proliferation, transformation and collagen synthesis / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the effects of interleukin-17 (IL-17) on the proliferation, transformation and collagen synthesis of the lung fibroblasts in mice with bleomycin-induced pulmonary fibrosis.</p><p><b>METHODS</b>In a mouse model of pulmonary fibrosis established by intratracheal administration of 5 mg/kg bleomycin, the dynamic expressions of IL-17/IL-17 receptor (IL-17R) mRNAs were detected by RT-PCR. At 14 days following bleomycin administration, the pulmonary fibroblasts were isolated, cultured and identified. MTT assay was used to assess the proliferation of the pulmonary fibroblasts in response to IL-17 treatment at different concentrations, and RT-PCR and Western blotting were employed to examine the mRNA and protein expressions of α-smooth muscle actin (α-SMA) and types I and III collagen.</p><p><b>RESULTS</b>IL-17/IL-17R mRNA levels were increased obviously in the pulmonary fibroblasts of rats with pulmonary fibrosis, and the highest expressions occurred at 14 days following bleomycin administration. Exogenous IL-17, at the optimal concentration of 50 ng/ml, significantly promoted the proliferation of the pulmonary fibroblasts in primary culture and obviously increased α-SMA expression and types I and III collagen synthesis in the fibroblasts.</p><p><b>CONCLUSION</b>IL-17 can promote the proliferation, transformation, and collagen synthesis of the pulmonary fibroblasts from rats with bleomycin-induced pulmonary fibrosis.</p>

Eukaryotic expression of human IL17-RD-ECD and generation of its monoclonal antibody / 生物工程学报

IL-17 Receptor D (IL-17 RD) is a cytokine receptor that mediates IL-17 signaling and plays an important role in responding to the invasion of extracellular pathogens and many inflammatory and autoimmune diseases such as rheumatoid arthritis. In this study we report the generation of a mouse monoclonal antibody against human IL-17 RD. The recombinant human IL-17RD extracellular domain (hIL-17RD-ECD) was produced in the baculovirus expression system and purified from culture medium of sf9 insect cells. The purified protein was used as a T-dependent antigen to immune Balb/C mice. B cells from the spleen of immunized mice were fused with murine cell SP2/0. Hybridoma cell lines were screened for the production of the monoclonal antibody against hIL-17-RD-ECD using ELISA. A hybridoma cell line 1F8 was found to have a high production of the antibody, which was further confirmed for the specificity by both western blot and ELISA analyses. The monoclonal antibody obtained from hybridoma 1F8 was characterized to be IgG1+Kappa subclass. This study provided a base for the further therapeutic application of the antibody on the autoimmune disease including rheumatoid arthritis.

Association between polymorphisms in Interleukin-17 receptor A gene and childhood IgA nephropathy / 소아과

PURPOSE: Interleukin-17 (IL-17) is produced by activated CD4+T cells and exhibits pleiotropic biological activity on various cell types. IL-17 was reported to be involved in the immunoregulatory response in IgA nephropathy (IgAN). Our aim was to investigate the association between single-nucleotide polymorphisms (SNPs) in IL-17 receptor A (IL-17RA) gene and childhood IgAN. METHODS: We analyzed the SNPs in the IL-17RA in 156 children with biopsy-proven IgAN and 245 healthy controls. We divided the IgAN patients into 2 groups and compared them with respect to proteinuria (4 mg/m2/h, 40 mg/m2/h, respectively) and the presence of pathological levels of biomarkers of diseases such as interstitial fibrosis, tubular atrophy, or global sclerosis. RESULTS: No difference was observed between the SNP genotypes rs2895332, rs1468488, and rs4819553 between IgAN patients and control subjects. In addition, no significant difference was observed between allele frequency of SNPs rs2895 332, rs1468488, and rs4819553 between patients in the early and advanced stage of the disease. However, significant difference was observed between the genotype of SNP rs2895332 between patients with proteinuria (>4 mg/m2/h) and those without proteinuria (codominant model OR 0.36, 95% CI 0.19-0.66, P<0.001; dominant model OR 0.35, 95% CI 0.17-0.69 P=0.002; recessive model OR 0.12, 95% CI 0.01-1.06 P=0.025). CONCLUSION: Our results indicate that the SNP in IL-17RA (rs2895332) may be related to the development of proteinuria in IgAN patients.

Expression and significance of interleukin-17 and its receptor in nasal polyps / 中华耳鼻咽喉头颈外科杂志

<p><b>OBJECTIVE</b>To detect the expression and distribution of interleukin-17 and interleukin 17 receptor (IL-17R) in nasal polyps and to probe into their significance in the pathology of nasal polyps.</p><p><b>METHODS</b>The methods of immunohistochemical staining and western blot were used to detect IL-17 and IL-17R in nasal polyps and controls.</p><p><b>RESULTS</b>In nasal polyp tissues, IL-17 expressed mainly in cytoplasm of plasm cell, less in prickle-cell layer of the epithelium and the acinus of the serous gland. In turbinates, IL-17 also expressed in the cytoplasm of the plasm cell, the prickle-cell layer of the epithelium and the acinus of the serous gland. The expression of IL-17 between nasal polyps and turbinates differed significantly (t = 2.237, 2.176, 2.246, P < 0.05, respectively). Both IL-17 and IL-17R displayed specific bands in nasal polyps and turbinates, but the bands of IL-17 and IL-17R in nasal polyps were stronger than those in turbinates.</p><p><b>CONCLUSIONS</b>IL-17 may have an important role in the occurrence of nasal polyps by specific combination with IL-17R and over-expression in nasal polyps.</p>