IL-29 enhances Toll-like receptor-mediated IL-6 and IL-8 production by the synovial fibroblasts from rheumatoid arthritis patientsReportar como inadecuado




IL-29 enhances Toll-like receptor-mediated IL-6 and IL-8 production by the synovial fibroblasts from rheumatoid arthritis patients - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

Arthritis Research and Therapy

, 15:R170

First Online: 29 October 2013Received: 09 March 2013Accepted: 11 October 2013

Abstract

IntroductionWe previously reported that IL-29, a newly described member of interferon IFN family, was overexpressed in blood and synovium of rheumatoid arthritis RA patients and triggered proinflammatory cytokine IL-6 and IL-8 mRNA expression in RA synovial fibroblasts RA-FLS. This suggests that IL-29 has an important role in synovial inflammation. Toll-like receptors TLRs also activate RA-FLS to produce inflammatory mediators including tumor necrosis factor α TNF-α and IL-1β in RA-FLS. Since the TLR family plays an early role in the innate immune response and the subsequent induction of the adaptive immune response, we hypothesize that IL-29 interacts with TLRs in RA inflammation. This study aimed to investigate the effect of IL-29 on TLR-mediated proinflammatory cytokine production in RA-FLS.

MethodsThe mRNA level of IL-29 receptors IL-28Rα and IL-10R2 in RA-FLS was determined by semi-quantitative RT- PCR. IL-6 and IL-8 mRNA expressions in RA-FLS were evaluated by real-time PCR after pre-incubation with IL-29 and subsequent stimulation with peptidoglycan PGN, TLR2 ligand, or polycytidylic acid polyI:C, TLR3 ligand, or lipopolysaccharide LPS, TLR4 ligand . The production of TLR2, 3, and 4 in RA-FLS after IL-29 stimulation was also assessed by real-time PCR and flow cytometry. IL-29 mRNA and protein expression in RA-FLS after stimulation with PGN, polyI:C, or LPS were measured by real-time PCR and enzyme-linked immunosorbent assay ELISA, respectively.

ResultsThe IL-29 receptor complex IL-28Rα and IL-10R2 was identified in RA-FLS. IL-29 enhanced TLR-mediated IL-6 and IL-8 expression in RA-FLS. IL-29 upregulated expression of TLR2, 3 and 4 in RA-FLS. Exposure to PGN, polyI:C or LPS triggered IL-29 production by RA-FLS.

ConclusionsWe show for the first time that IL-29 enhances TLR-induced proinflammatory cytokine production in RA-FLS via upregulation of TLRs.

AbbreviationsDMEMDulbecco’s modified Eagle’s medium

ELISAEnzyme-linked immunosorbent assay

FBSFetal bovine serum

FLSSynovial fibroblast

IFNInterferon

ILInterleukin

PCRPolymerase chain reaction

RARheumatoid arthritis

RA- TLRToll-like receptor

TNF-αTumor necrosis factor α.

Electronic supplementary materialThe online version of this article doi:10.1186-ar4357 contains supplementary material, which is available to authorized users.

Lingxiao Xu, Xiaoke Feng contributed equally to this work.

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Autor: Lingxiao Xu - Xiaoke Feng - Wenfeng Tan - Weijuan Gu - Dunming Guo - Miaojia Zhang - Fang Wang

Fuente: https://link.springer.com/







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