Pristane primed rat T cells enhance TLR3 expression of fibroblast-like synoviocytes via TNF-α initiated p38 MAPK and NF-κB pathways

Based on pristane-induced arthritis (PIA), we found that T cells mediate TLR3 overexpression in fibroblast-like synoviocytes (FLS). The aim of this study is to determine key factors by which T cells induce TLR3 expression. Rat FLS were co-cultured with pristane primed T cell conditioned medium (PPT medium), and TLR3 expression of FLS was significantly induced. TNF-alpha, IFN-gamma and IL-17 were dominantly expressed in PIA T cells. The overexpression of TLR3 and its related genes in FLS co-cultured with PPT medium could be reduced through blocking TNF-alpha pathway. CD4(+) T cells from spleen of PIA rats showed increase of TNF-alpha. secretion. P38 MAPK and NF-kappa B were activated in FLS by PPT medium, and their inhibitors decreased TLR3 upregulation significantly. Finally, TNF-alpha induced TLR3 expression was confirmed in human synovial cells. Summarily, TNF-alpha derived from pristane primed T cells induced TLR3 expression of FLS through activating p38 MAPK and NF-kappa B pathways. (C) 2014 Elsevier Inc. All rights reserved.