Objective The objective is to examine the effect of tumor necrosis factor α (TNFα) on apoptosis and proliferation of rheumatoid arthritis synovial fibroblasts (RASFs) and to elucidate the regulatory roles of Kruppel-like factor 4 (KLF4) in TNFα-induced RASF apoptosis. Methods Changes in cell proliferation were measured using an 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-di- phenytetrazoliumromide (MTT) assay, and changes in cell apoptosis were detected by flow cytometry and Hoechst 33258 staining. Changes in the apoptosis-related protein caspase-3 and the apoptosis-related genes bcl-2/bax were measured by western blot and real-time PCR, respectively Results TNFα stimulation increased cell proliferation ( p < 0.05), decreased cell apoptosis ( p < 0.05), declined caspase-3 expression ( p < 0.05), and upregulated bcl-2/bax level ( p < 0.05) in RASFs. KLF4 gene silencing decreased cell proliferation ( p < 0.05), increased cell apoptosis ( p < 0.05), upregulated caspase-3 expression ( p < 0.05), and downregulated bcl-2/bax level ( p < 0.05) induced by TNFα in RASFs. Conclusions TNFα caused a decrease in RASF apoptosis, and KLF4 promoted resistance to TNFα-induced apoptosis and cell proliferation.
Blocking ERK-1/2 reduces tumor necrosis factor α-induced interleukin-18 bioactivity in rheumatoid arthritis synovial fibroblasts by induction of interleukin-18 binding protein A
