Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi 710061, China; Key Laboratory of Environment and Genes Related to Diseases, Xi'an Jiaotong University, Ministry of Education, Xi'an, Shaanxi 710061, China.
Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi 710061, China.
Clin Immunol. 2015 Feb;156(2):141-53. doi: 10.1016/j.clim.2014.11.008. Epub 2014 Dec 19.
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-α, IFN-γ 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-α pathway. CD4(+) T cells from spleen of PIA rats showed increase of TNF-α secretion. P38 MAPK and NF-κB were activated in FLS by PPT medium, and their inhibitors decreased TLR3 upregulation significantly. Finally, TNF-α induced TLR3 expression was confirmed in human synovial cells. Summarily, TNF-α derived from pristane primed T cells induced TLR3 expression of FLS through activating p38 MAPK and NF-κB pathways.
基于十六烷醇诱导性关节炎（PIA），我们发现 T 细胞介导成纤维样滑膜细胞（FLS）中 TLR3 的过度表达。本研究旨在确定 T 细胞诱导 TLR3 表达的关键因素。用十六烷醇预刺激的 T 细胞条件培养基（PPT 培养基）与大鼠 FLS 共培养，可显著诱导 FLS 中 TLR3 的表达。在 PIA T 细胞中，TNF-α、IFN-γ 和 IL-17 表达占优势。通过阻断 TNF-α 通路，可减少与 PPT 培养基共培养的 FLS 中 TLR3 及其相关基因的过度表达。PIA 大鼠脾脏中的 CD4(+)T 细胞表现出 TNF-α 分泌增加。PPT 培养基可激活 FLS 中的 p38 MAPK 和 NF-κB，其抑制剂可显著降低 TLR3 的上调。最后，在人滑膜细胞中证实了 TNF-α 诱导的 TLR3 表达。综上所述，来自十六烷醇预刺激 T 细胞的 TNF-α 通过激活 p38 MAPK 和 NF-κB 通路诱导 FLS 中 TLR3 的表达。
