Toll-like receptor-9 is involved in the development of B cell stimulating factor-induced systemic lupus erythematosus.

Abstract

The objective of the present study was to investigate the role of Toll-like receptor (TLR)-9 in B lymphocyte stimulating factor (BLyS)-induced systemic lupus erythematosus (SLE) in mice. The anti-double stranded (ds)DNA antibody titer, levels of complement proteins (C3 and C4), interleukin (IL)-10 and the disease activity [assessed by the erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) level] were measured. A total of 21 transgenic female mice (aged 8-10 weeks and weighing 30-40 g) expressing the Epstein-Barr virus membrane antigen, BLLF1, were studied. Mice were randomly divided into the control, the BLyS inhibition and the TLR-9 inhibition groups, with 7 mice in each group. Mice in the blank control group received intraperitoneal injections of normal saline, mice in the BLyS inhibition group received intraperitoneal injections of anti-BR3 monoclonal antibody (5,000 ng/day) and mice in the TLR-9 inhibition group received intraperitoneal injections of anti-human TLR-9 antibody (250 ng/day). The treatment regimens continued for 10 days, followed by the collection of peripheral venous blood. The relative levels of TLR-9 mRNA were measured by reverse transcription-quantitative polymerase chain reaction. Furthermore, the BLyS protein concentration and IL-10 levels were measured by ELISA. TLR-9 mRNA, BLyS, IL-10, anti-dsDNA antibody titer, C3, C4, ESR and CRP levels of the blank control group were significantly higher than those of the other two groups (P<0.05). The differences in comparison of these indexes between the BLyS inhibition and TLR-9 inhibition groups were not statistically significant (P>0.05), with the exception of TLR-9 mRNA and BLyS. In conclusion, the TLR-9 signaling pathway may be important for BLyS-induced SLE, and regulation of the inflammatory immune level.