Activation of LXR attenuates collagen-induced arthritis via suppressing BLyS production

- Administration of GW3965 suppressed BLyS production to ameliorate CIA in DBA/1 mice.
- GW3965 inhibited the basal and IFNγ/TGFβ-induced BLyS expression in vitro.
- Activation of LXR suppressed NF-κB binding to the promoter region of BLyS gene.
- GW3965 repressed IFNγ-induced STAT1 activation and TGFβ-induced SMAD3 activation.

ABSTRACTB-lymphocyte stimulator (BLyS) plays a critical role in the pathogenesis and progression of rheumatoid arthritis (RA). Liver X receptor (LXR), a nuclear receptor, has an important anti-inflammatory effect. However, it is unclear whether the BLyS expression is regulated by LXR. In this study, we found that treatment with LXR agonist in collagen-induced arthritis (CIA) mice significantly attenuated arthritis progression, and markedly decreased BLyS production in serum and splenocytes as well as the production of serum IFNγ and TGFβ. Activation of LXR in B lymphocytes dramatically suppressed the basal and IFNγ/TGFβ-induced BLyS expression. Moreover, LXR agonist prominently suppressed the binding of NF-κB to BLyS promoter region, and decreased the promoter's transcriptional activity. Additionally, activation of LXR obviously repressed IFNγ-induced STAT1 activation and TGFβ-induced SMAD3 activation. These results indicated that downregulation of BLyS may be a novel mechanism by which LXR ameliorates RA, and LXR/BLyS pathway may serve as a novel target for the treatment of RA.