• Title, Summary, Keyword: IL-17A

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Cigarette Smoke Extract Enhances IL-17A-Induced IL-8 Production via Up-Regulation of IL-17R in Human Bronchial Epithelial Cells

  • Lee, Kyoung-Hee;Lee, Chang-Hoon;Woo, Jisu;Jeong, Jiyeong;Jang, An-Hee;Yoo, Chul-Gyu
    • Molecules and Cells
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    • v.41 no.4
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    • pp.282-289
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    • 2018
  • Interleukin-17A (IL-17A) is a pro-inflammatory cytokine mainly derived from T helper 17 cells and is known to be involved in the pathogenesis of chronic obstructive pulmonary disease (COPD). Cigarette smoke (CS) has been considered as a primary risk factor of COPD. However, the interaction between CS and IL-17A and the underlying molecular mechanisms have not been clarified. In the current study, we investigated the effects of cigarette smoke extract (CSE) on IL-17A-induced IL-8 production in human bronchial epithelial cells, and sought to identify the underlying molecular mechanisms. IL-8 production was significantly enhanced following treatment with both IL-17A and CSE, while treatment with either IL-17A or CSE alone caused only a slight increase in IL-8 production. CSE increased the transcription of IL-17RA/RC and surface membrane expression of IL-17R, which was suppressed by an inhibitor of the phosphoinositide 3-kinase (PI3K)/Akt pathway (LY294002). CSE caused inactivation of glycogen synthase $kinase-3{\beta}$ ($GSK-3{\beta}$) via the PI3K/Akt pathway. Blockade of $GSK-3{\beta}$ inactivation by overexpression of constitutively active $GSK-3{\beta}$ (S9A) completely suppressed the CSE-induced up-regulation of IL-17R expression and the CSE-induced enhancement of IL-8 secretion. In conclusion, inactivation of $GSK-3{\beta}$ via the PI3K/Akt pathway mediates CSE-induced up-regulation of IL-17R, which contributes to the enhancement of IL-17A-induced IL-8 production.

Elevated Serum IL-17A but not IL-6 in Glioma Versus Meningioma and Schwannoma

  • Doroudchi, Mehrnoosh;Pishe, Zahra Ghanaat;Malekzadeh, Mahyar;Golmoghaddam, Hossein;Taghipour, Mousa;Ghaderi, Abbas
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.9
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    • pp.5225-5230
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    • 2013
  • Background: There is a Th1/Th2 cytokine imbalance and expression of IL-17 in patients with brain tumours. We aimed to compare the levels of IL-17A and IL-6 in sera of glioma, meningioma and schwannoma patients as well as in healthy individuals. Materials and Methods: IL-17A and IL-6 levels were measured in sera of 38 glioma, 24 meningioma and 18 schwannoma patients for comparison with 26 healthy controls by commercial ELISA assays. Results: We observed an increase in the IL-17A in 30% of glioma patients while only 4% and 5.5% of meningioma and schwannoma patients and none of the healthy controls showed elevated IL-17A in their sera ($0.29{\pm}0.54$, $0.03{\pm}0.15$ and $0.16{\pm}0.68$ vs. $0.00{\pm}0.00pg/ml$; p=0.01, p=0.01 and p=0.001, respectively). There was also a significant decrease in the level of IL-6 in glioma patients compared to healthy controls ($2.34{\pm}4.35$ vs. $4.67{\pm}4.32pg/ml$; p=0.01). There was a direct correlation between the level of IL-17A and age in glioma patients (p=0.005). Glioma patients over 30 years of age had higher IL-17A and lower IL-6 in their sera compared to the young patients. In addition, a non-significant grade-specific inverse trend between IL-17A and IL-6 was observed in glioma patients, where high-grade gliomas had higher IL-17A and lower IL-6. Conclusions: Our data suggest a Th17 mediated inflammatory response in the pathogenesis of glioma. Moreover, tuning of IL-6 and IL-17A inflammatory cytokines occurs during progression of glioma. IL-17A may be a potential biomarker and/or immunotherapeutic target in glioma cases.

Association between Polymorphisms of Interleukin-17A and Interleukin-17F Genes and Silicosis Susceptibility in Chinese Han People

  • Chen, Ying;Fan, Xue-Yun;Jin, Yu-Lan;Yao, San-Qiao;Yun, Xiang;Hua, Zheng-Bing;Shen, Fu-Hai
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.20
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    • pp.8775-8778
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    • 2014
  • Background: To explore the relationship between polymorphisms of interleukin17 (IL-17) gene(A-832G 7488A/G) and the susceptibility to silicosis, a risk factor for lung cancer. Materials and Methods: A total of 113 silicosis patients and 116 workers without silicosis were enrolled in the case-control study. IL-17A A-832G and IL-17F 7488A/G polymorphisms were evaluated by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Results: The frequencies of AA,GG and AG of IL-17A A-832G locus in the case and control groups were 46.9%, 8.0%, 45.1%, and 49.2%, 7.6%, 43.2%, respectively, with no significant differences (p>0.05).The GG genotype in the IL-17F (7488A/G) locus was not found. The frequencies of AA and GA of IL-17F 7488A/G locus in the case and control groups were 84.1%, 15.9% and 66.4%, 33.6%, respectively (p<0.05). Analysis of combined effects showed that the individuals with GG+AG genotype of IL-17A and GG+GA genotype of IL-17F are protected against silicosis (OR=0.469). Conclusions: IL-17F 7488A/G is associated with susceptibility to silicosis, and G allele may have a protective effect. No relationship was found between IL-17A gene polymorphisms at A-832G and silicosis.

Meta-analysis of Associations between Interleukin-17 Gene Polymorphisms and Risk of Gastric Cancer

  • Yu, Hui;Sun, Si;Liu, Fang;Xu, Qing-Hua
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.20
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    • pp.8709-8713
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    • 2014
  • Background: Previous studies have indicated that single nucleotide polymorphisms (SNPs) of the interleukin-17 (IL-17) gene are associated with an increased risk of gastric cancer. However, the findings were inconsistent. Materials and Methods: To provide a more reliable estimation of the association between SNPs in the IL-17 gene and the susceptibility to gastric cancer, we searched PubMed, CNKI, and Wan Fang databases and selected finally six studies covering 2,366 cases and 3,205 controls to perform a meta-analysis. Results: Statistical analyses showed that an rs2275913 polymorphism within the IL-17A gene was significantly associated with an increased risk of gastric cancer using a generalized odds ratio (ORG, a model-free approach). Moreover, we also found that the 'A' allele carriers of IL-17A rs2275913 had a significant link with clinicopathological features. However, no significant positive signals were observed in the association analysis of the rs3748067 and rs763780 polymorphisms with the risk of gastric cancer in IL-17A and IL-17F, respectively. Conclusions: Despite some limitations, the present meta-analysis provided a more precise estimation of the relationship between the IL-17 gene SNPs and gastric cancer risk compared with individual studies.

The Role of IL-17 in a Lipopolysaccharide-Induced Rhinitis Model

  • Bae, Jun-Sang;Kim, Ji-Hye;Kim, Eun Hee;Mo, Ji-Hun
    • Allergy, Asthma & Immunology Research
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    • v.9 no.2
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    • pp.169-176
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    • 2017
  • Purpose: Lipopolysaccharide (LPS) is a cell wall component of Gram-negative bacteria and important for pro-inflammatory mediators. This study aimed to establish a rhinitis model using ovalbumin (OVA) and LPS in order to evaluate the role of interleukin (IL)-17 in the pathogenesis of an LPS-induced non-eosionophilic rhinitis model. Methods: Mice were divided into 4 groups and each group consisted of 10 mice (negative control group, allergic rhinitis model group, $1-{\mu}g$ LPS treatment group, and $10-{\mu}g$ LPS treatment group). BALB/c mice were sensitized with OVA and 1 or $10{\mu}g$ of LPS, and challenged intranasally with OVA. Multiple parameters of rhinitis were also evaluated to establish the LPS-induced rhinitis model. IL-17 knockout mice were used to check if the LPS-induced rhinitis model were dependent on IL-17. Eosinophil and neutrophil infiltration, and mRNA and protein expression profiles of cytokine in nasal mucosa or spleen cell culture were evaluated using molecular, biochemical, histopathological, and immunohistological methods. Results: In the LPS-induced rhinitis model, neutrophil infiltration increased in the nasal mucosa, and systemic and nasal IL-17 and interferon-gamma ($IFN-{\gamma}$) levels also increased as compared with the OVA-induced allergic rhinitis model. These findings were LPS-dose-dependent. In IL-17 knockout mice, those phenotypes (neutrophil infiltration, IL-17, and $IFN-{\gamma}$) were reversed, showing IL-17 dependency of LPS-induced rhinitis. The expression of vascular endothelial growth factor (VEGF), an important mediator for inflammation and angiogenesis, decreased in IL-17 knockout mice, showing the relationship between IL-17 and VEGF. Conclusions: This study established an LPS-induced rhinitis model dependent on IL-17, characterized by neutrophil infiltration and increased expression of IL-17.

The Th17 and Autoimmune Arthritis (Th17과 자가면역 관절염)

  • Cho, Mi-La;Heo, Yu-Jung;Park, Jin-Sil;Lee, Seon-Yeong;Sung, Young-Chul;Kim, Ho-Youn
    • IMMUNE NETWORK
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    • v.7 no.1
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    • pp.10-17
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    • 2007
  • Autoimmune arthritis, such as rheumatoid arthritis (RA), is a chronic inflammatory disorder that primarily affects the joints and then results in their progressive destruction. Effector Th cells have been classified as Th1 and Th2 subsets based on their cytokine expression profiles and immune regulatory function. Another subset of T cells termed Th17 was recendy discovered and known to selectively produce IL-17. Also, Th17 was shown to be generated by TGF${\beta}$ and IL-6 and maintained by IL-23. IL-17 is a proinflammatory cytokine that is considered to involve the development of various inflammatory autoimmune diseases such as RA, asthma, lupus, and allograft rejection. IL-17 is present in the sera, synovial fluids and synovial biopsies of most RA patient. IL-17 activates RA synovial fibroblasts to synthesize IL-6, IL-8 and VEGF via PI3K/Akt and NF-${\kappa}B$ dependent pathway. IL-17 increases IL-6 production, collagen destruction and collagen synthesis. In addition, it not only causes bone resorption but also increases osteoclastogenesis and fetal cartilage destruction. Inhibition of the IL-17 production may contribute a novel therapeutic approach along with potent anti-inflammatory effect and with less immunosuppressive effect on host defenses.

IL-17A Levels in the Sera of Patients with Gastric Cancer Show Limited Elevation

  • Malek-Hosseini, Zahra;Taherinejad, Marziye;Malekzadeh, Mahyar;Ghaderi, Abbas;Doroudchi, Mehrnoosh
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.16
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    • pp.7149-7153
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    • 2015
  • Background: Inflammation plays a major role in the development and progression of gastric and other gastrointestinal tumors. The IL-17 family of cytokines has been under investigation as targets of immunotherapy. Materials and Methods: We investigated the levels of IL-17A inflammatory cytokine in the sera of 57 patients with gastric cancer (GC) and 90 healthy age/sex matched controls using ELISA methods. Results: In only 5 (8.8%) of the patients' sera was IL-17A detectable. No IL-17A was apparent in the sera of healthy controls. The maximum concentration of IL-17A in patients was 7.004 pg/ml. Vascular and lymphatic invasions were only seen in one of the 5 positive cases. Although all of them were in the age group >60 years, no correlation was seen between age and IL-17A level. These results are somewhat different from our findings for colorectal cancer (CRC) in the same population. Conclusions: It is possible that the inflammopathology of CRC and GC are rather different, at least in Fars, a southern province of Iran.

Studies of Xanthium strumarium Extract Suppressing Th17-cell Differentiation and Anti-dermatitic Effect in BMAC-induced Atopy Dermatitis of NC/Nga Mice (창이자 추출물이 아토피 피부염 유발 생쥐의 비장 세포 Th17의 세포분화 억제에 따른 아토피 피부 상태에 미치는 영향)

  • Kim, Kum-Lan;Choe, Tae-Boo
    • KSBB Journal
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    • v.24 no.4
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    • pp.383-392
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    • 2009
  • Xanthii fructus which is well known as "Chang-ihjah" in Korea is the dried fruit of Xanthium strumarium L. (or Xanthium sibiricum PATR. Ex WIDD., Asteraceae. XS). Water extract of this fruit has been used for treatment of various inflammatory diseases such as tympanitis, allergic rhinitis, or ozena as alternative therapy material usually by oral administration in far Eastern countries including Korea. In this study, the effect of XS extract (XS-E) or XS-30% acetone fraction layer (XS-30% AFL) on the differentiation of $CD4^+$ T cells isolated from NC/Nga mouse and the production of IL-17 was investigated. The experimental results showed that $100\;{\mu}g$/mL of XS-E could decrease the production of IL-17 by $CD4^+$ Th17 cells by 2 fold and only $20\;{\mu}g$/mL of XS-30% AFL could inhibit 3.5 fold. The amount of IL-17A and IL-22 mRNA determined by real-time PCR was decreased remarkably when XS-E or XS-30% AFL was treated on $CD4^+$ Th17 cells(p<0.01, p<0.001). The amount of IL-17A protein determined by ELISA was also decreased remarkably(p<0.05, p<0.001). To study the effect of XS-E or XS-30% AFL on the proliferation of Th17 cells, $CD4^+$ T cells of a NC/Nga mouse was firstly differentiated by rIL-6/TGF-$\beta$ and then stimulated by rIL-23. The control group of Th17 cells were doubled every each day, while those of XS-E or XS-30% AFL treated group were shown to be delayed remarkably by these extracts. In conclusion, XS can inhibit the differentiation of Th17 cells of NC/Nga mouse and the production of IL-17 successfully, which may be a beneficial result for the treatment of atopic skin dermatitis.

Interleukin 17-expressing Innate Synovial Cells Drive K/BxN Serum-induced Arthritis

  • Cho, Wang Sik
    • Proceedings of the Korea Contents Association Conference
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    • pp.551-552
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    • 2018
  • K/BxN serum can induce arthritis in normal mice because of abundant autoantibodies that trigger an innate inflammatory response in joints. To determine whether IL-17 is involved in the pathogenesis of serum-induced arthritis, we injected wild-type and $IL-17^{-/-}$ mice with K/BxN serum and evaluated them for signs of arthritis. Unlike wild-type mice, $IL-17^{-/-}$ mice did not show any signs of arthritis. IL-17 was produced predominantly by $CD3^-CD4^-gdTCR^-NK1.1^-Sca1^{int}Thy1^{hi}$ cells residing in the inflamed synovial tissue. When synovial cells extracted from normal joints were stimulated with IL-23 or autoantibody-containing immune complexes, a substantial fraction of $Sca1^{int}Thy1^{hi}$ cells produced IL-17. Thus, we have identified a novel population of IL-17-producing innate synovial cells that play a crucial role in the development of K/BxN serum-induced arthritis.

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IL-23 P19 Expression Induced by IL-17 and $IL-1{\beta}$ in Rheumatoid Arthritis Synovial Mononuclear Cells (류마티스관절염 환자의 활액 세포에서 IL-17과 $IL-1{\beta}$에 의한 IL-23p19의 발현 증가)

  • Cho, Mi-La;Heo, Yu-Jung;Oh, Hye-Jwa;Kang, Chang-Min;Lee, Seon-Yeong;Hong, Yeon-Sik;Kim, Ho-Youn
    • IMMUNE NETWORK
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    • v.8 no.1
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    • pp.29-37
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    • 2008
  • Interleukin-23 (IL-23) is a novel pro-inflammatory cytokine which has been implicated to play a pathogenic role in rheumatoid arthritis (RA). This study was undertaken to investigate the IL-23 inductive activity of the proinflammatory cytokine IL-17, $IL-1{\beta}$ and tumor necrosis factor (TNF-${\alpha}$) in RA synovial fluid mononuclear cells (SFMC). Expression of IL-23p19, IL-17, $IL-1{\beta}$ and TNF-${\alpha}$ in joint was examined by immunohistochemistry (IHC) of patients with RA and osteoarthritis (OA). The effects of IL-17 and $IL-1{\beta}$ on expression of IL-23p19 in human SFMC from RA patients were determined by reverse transcriptase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA). IL-23p19 was expressed in the RA fibroblast like synoviocyte (FLS), but not from OA FLS. Similar to the protein expression, IL-23p19 mRNA could be detected by RT-PCR in RA SFMC. IL-17 and $IL-1{\beta}$ could induce RA SFMC to produce the IL-23p19. The effects of IL-17 were much stronger than $IL-1{\beta}$ or TNF-${\alpha}$. These responses were observed in a doseresponsive manner. In addition, IL-17 or $IL-1{\beta}$ neutralizing antibody down-regulated the expression of IL-23p19 induced by LPS in RA-SFMC. Our results demonstrate that IL-23p19 is overexpressed in RA synovium and IL-17 and $IL-1{\beta}$ appears to upregulate the expression of IL-23p19 in RA-SFMC.