PMID- 23078630 OWN - NLM STAT- MEDLINE DCOM- 20150721 LR - 20240109 IS - 1478-6362 (Electronic) IS - 1478-6354 (Print) IS - 1478-6354 (Linking) VI - 14 IP - 5 DP - 2012 Oct 19 TI - Interleukin-29 modulates proinflammatory cytokine production in synovial inflammation of rheumatoid arthritis. PG - R228 LID - 10.1186/ar4067 [doi] AB - INTRODUCTION: The immunoregulatory function of interleukin (IL)-29 has recently been recognized. However, little is known about the involvement of IL-29 in the pathogenesis of rheumatoid arthritis (RA). This study aimed to examine the expression profiles of IL-29 in blood, synovial fluid (SF) and synovium in RA patients and investigate the effect of IL-29 on cytokines production in RA synovial fibroblasts. METHODS: The transcript levels of IL-29 and its specific receptor IL-28Ralpha in peripheral blood mononuclear cells (PBMC) and synovium were determined by real-time reverse transcription-polymerase chain reaction (real-time PCR). The concentrations of IL-29 in serum and synovial fluid (SF) were quantified by enzyme-linked immunoassay (ELISA), and the correlation of serum IL-29 levels with disease activity in RA patients was investigated. Furthermore, the expression of IL-29 in RA synovium was examined by immunohistochemistry and double immunofluorescence analysis. Finally, the expression of IL-6, IL-8, IL-10, IL-17 and matrix metalloproteinase-3 (MMP-3) in synovial fibroblasts upon IL-29 stimulation was determined by real-time PCR. RESULTS: IL-29 and IL-28Ralpha mRNA expression in PBMC was significantly increased in patients with RA compared with healthy controls (HC). The serum levels of circulating IL-29 were higher in RA than those in HC. Increased IL-29 levels were detected in RA SF when compared with osteoarthritis (OA) SF. However, serum IL-29 levels showed no significant correlation with RA disease activity. IL-29 was mostly expressed in the lining region of RA synovium. Moreover, IL-29 was expressed predominately in synovial macrophages and fibroblasts. RA synovial fibroblasts exposed to IL-29 specifically upregulated IL-6, -8 and MMP-3 but downregulated IL-10. CONCLUSIONS: The findings in the present study indicate, for the first time, that IL-29 is dysregulated in patients with RA, which may contribute to the RA pathogenesis via inducing the production of proinflammatory cytokines, chemokines or matrix metalloproteinases in synovial fibroblasts. FAU - Wang, Fang AU - Wang F FAU - Xu, Lingxiao AU - Xu L FAU - Feng, Xiaoke AU - Feng X FAU - Guo, Dunming AU - Guo D FAU - Tan, Wenfeng AU - Tan W FAU - Zhang, Miaojia AU - Zhang M LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20121019 PL - England TA - Arthritis Res Ther JT - Arthritis research & therapy JID - 101154438 RN - 0 (Cytokines) RN - 0 (interferon-lambda, human) RN - 0 (Interleukins) RN - 0 (Receptors, Cytokine) RN - 0 (interleukin 28alpha receptor) RN - 9008-11-1 (Interferons) RN - EC 3.4.24.17 (Matrix Metalloproteinase 3) SB - IM MH - Adolescent MH - Adult MH - Aged MH - Aged, 80 and over MH - Arthritis, Rheumatoid/*metabolism/pathology MH - Case-Control Studies MH - Cells, Cultured MH - Cytokines/*metabolism MH - Female MH - Fibroblasts/drug effects/metabolism/pathology MH - Humans MH - Interferons MH - Interleukins/*metabolism/pharmacology MH - Male MH - Matrix Metalloproteinase 3/metabolism MH - Middle Aged MH - Osteoarthritis/metabolism/pathology MH - Receptors, Cytokine/metabolism MH - Severity of Illness Index MH - Synovial Fluid/metabolism MH - Synovial Membrane/*metabolism MH - Synovitis/*metabolism MH - Young Adult PMC - PMC3580539 EDAT- 2012/10/20 06:00 MHDA- 2015/07/22 06:00 PMCR- 2012/10/19 CRDT- 2012/10/20 06:00 PHST- 2012/06/28 00:00 [received] PHST- 2012/10/09 00:00 [accepted] PHST- 2012/10/20 06:00 [entrez] PHST- 2012/10/20 06:00 [pubmed] PHST- 2015/07/22 06:00 [medline] PHST- 2012/10/19 00:00 [pmc-release] AID - ar4067 [pii] AID - 10.1186/ar4067 [doi] PST - epublish SO - Arthritis Res Ther. 2012 Oct 19;14(5):R228. doi: 10.1186/ar4067.