title: IL-29 enhances Toll-like receptor-mediated IL-6 and IL-8 production by the synovial fibroblasts from rheumatoid arthritis patients.
abstract: BACKGROUND
  We 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.
  
  
  METHODS
  The 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 (poly(I: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, poly(I:C), or LPS were measured by real-time PCR and enzyme-linked immunosorbent assay (ELISA), respectively.
  
  
  RESULTS
  The 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, poly(I:C) or LPS triggered IL-29 production by RA-FLS.
  
  
  CONCLUSIONS
  We show for the first time that IL-29 enhances TLR-induced proinflammatory cytokine production in RA-FLS via upregulation of TLRs.
authors.forename: Lingxiao
authors.initials: L
authors.lastname: Xu
authors.forename: Xiaoke
authors.initials: X
authors.lastname: Feng
authors.forename: Wenfeng
authors.initials: W
authors.lastname: Tan
authors.forename: Weijuan
authors.initials: W
authors.lastname: Gu
authors.forename: Dunming
authors.initials: D
authors.lastname: Guo
authors.forename: Miaojia
authors.initials: M
authors.lastname: Zhang
authors.forename: Fang
authors.initials: F
authors.lastname: Wang
mesh_terms: D001172:Arthritis, Rheumatoid / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002460:Cell Line; D004797:Enzyme-Linked Immunosorbent Assay; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D005434:Flow Cytometry; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007372:Interferons; D015850:Interleukin-6 / Q000235:genetics* / Q000378:metabolism; D016209:Interleukin-8 / Q000235:genetics* / Q000378:metabolism; D007378:Interleukins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D010457:Peptidoglycan / Q000494:pharmacology; D011070:Poly I-C / Q000494:pharmacology; D018121:Receptors, Cytokine / Q000235:genetics / Q000378:metabolism; D053701:Receptors, Interleukin-10 / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013583:Synovial Membrane / Q000378:metabolism / Q000473:pathology; D051195:Toll-Like Receptor 2 / Q000819:agonists / Q000235:genetics* / Q000378:metabolism; D051196:Toll-Like Receptor 3 / Q000819:agonists / Q000235:genetics* / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000819:agonists / Q000235:genetics* / Q000378:metabolism; D000095022:Interferon Lambda
chemical_list: D007372:Interferons; D015850:Interleukin-6; D016209:Interleukin-8; D007378:Interleukins; D008070:Lipopolysaccharides; D010457:Peptidoglycan; D011070:Poly I-C; D018121:Receptors, Cytokine; D053701:Receptors, Interleukin-10; D051195:Toll-Like Receptor 2; D051196:Toll-Like Receptor 3; D051197:Toll-Like Receptor 4; C000624353:interferon-lambda, human; D000095022:Interferon Lambda; C471046:interleukin 28alpha receptor