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  • Title: Activation of farnesoid X receptor attenuates liver injury in systemic lupus erythematosus.
    Author: Lian F, Wang Y, Chen J, Xu H, Yang X, Liang L, Zhan Z, Ye Y, Chen M.
    Journal: Rheumatol Int; 2012 Jun; 32(6):1705-10. PubMed ID: 21431940.
    Abstract:
    To investigate the expression and effect of farnesoid X receptor (FXR) on systemic lupus erythematosus (SLE) liver dysfunction and indicate its hepatoprotective role and the immunomodulatory property. mRNA and protein levels of FXR were determined on the liver specimens of SLE patients with liver injury as well as MRL/lpr rodent models. The FXR agonist chenodeoxycholic acid (CDCA) was administrated to MRL/lpr mice and the control BALB/C with concanavalin A (ConA)-induced liver injury. Blood samples were taken 0, 4, 8, 12, 16, and 24 h after ConA injection for the detection of serum ALT, AST, IFN-γ, TNF-α, and IL-6. FXR was down-regulated at both mRNA and protein levels in the liver specimens of SLE patients with liver injury as well as MRL/lpr mice. MRL/lpr was more susceptible to ConA than BALB/C indicated by significantly higher levels of aminotransferase and inflammatory cytokines. Activation of FXR by CDCA significantly reduced aminotransferase and inflammatory cytokines IFN-γ, TNF-α, and IL-6 caused by ConA injection in MRL/lpr mice. FXR was down-regulated in SLE patients as well as MRL/lpr lupus models with liver dysfunction. FXR activation ameliorated liver injury and suppressed inflammatory cytokines, thereby showing its protective function in SLE. Our findings raised the promising potential target for the treatment of SLE liver injury.
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