In the present study, we show for the first time that TLR2, TLR3 and TLR4 engagement on RA-FLS induces endogenous IL-29, which further enhances IL-6 and IL-8 expression by upregulation of TLR2, TLR3 and TLR4 expression. This evidence concerns the gene TLR4 and rheumatoid arthritis.