Mechanism of IL-38 inhibits LPS/TLR4 induced inflammation in patients with rheumatoid arthritis / 中国免疫学杂志

ABSTRACT

Objective:To investigate the proteins association of IL-38 and TLR4 in rheumatoid arthritis (RA) and its mechanism in RA pathogenesis.Methods:Forty-one rheumatoid arthritis patients(observation group) and forty-five patients with post-traumatic synovial membrane resection (control group) in our hospital from Jan 2013 to Feb 2016 were selected as study subjects.Peripheral blood mononuclear cells (PBMCs),synovial tissues and serum from patients with RA and controls were collected.The expression of IL-38 and TLR4 in PBMCs and synovial tissues were detected by real-time polymerase chain reaction (realtime-PCR).The protiens of IL-38 and TLR4 in synovial tissues and fluid from RA patients and controls were detected by enzyme-linked immunosorbent assay (ELISA) or Western blot assay,respectively.RAW264.7 cells were stimulated by lipopolysaccharide (LPS) and/or IL-38.The production of inflammatory cytokines including IL-6,IL-8 as well as TNF-α were detected by real-time-PCR and ELISA,respectively.The activation of nuclear factor-κB(NF-κB) signaling were determined by nuclear transfer reagent kit for NF-κB and Western blot.Results: Compared with control group,the expression of IL-38 in PBMCs,synovial tissue,serum and synovial fluid of patients with RA increased significantly,meanwhile,TLR4 was significantly increased in PBMCs and synovium of RA patients.Moreover,IL-38 was negatively associated with TLR4 in RA,suggested by Pearson′s correlation analysis.When RAW264.7 cells were stimulated by LPS with or without IL-38 in vitro,IL-38 could suppress LPS-mediated expression of TLR4 and the production of IL-6,IL-8 and TNF-α in RAW264.7 cells.IL-38 can inhibit the activation of NF-κB signaling pathway,so we hypothesized that IL-38 may inhibit the expression of inflammatory factor which induced by LPS/TLR4 signaling via inhibiting the activation of NF-κB signaling pathway.Conclusion: IL-38 can attenuates rheumatoid arthritis through inhibiting LPS/TLR4 induced inflammation in rheumatoid arthritis,and the mechanism may be through inhibiting the activation of NF-κB signaling pathway.