Mechanism of TGF‑β1 inhibiting Kupffer cell immune responses in cholestatic cirrhosis

Abstract

Effect of exogenous transforming growth factor-β1 (TGF-β1) on cholestatic mice by inhibiting Kupffer cell immune responses in liver was investigated. To induce cholestasis, BALB/c mice received a sham operation (Mock group), or underwent a bile duct ligation (BDL group) and then were subcutaneously injected with TGF-β1 at multiple sites (TGF group). Liver functions were evaluated according to the levels of alanine aminotransferase (ALT), aspartate aminotransferase AST and γ-glutamyltranspeptidase (γ-GT) in serum samples. Expression of nuclear factor-κB (NF-κB), interleukin-6 (IL-6), IL-1β and tumor necrosis factor-α (TNF-α) was detected. Expression of inducible nitric oxide synthase (iNOS) and arginase-1 (Arg-1) in Kupffer cells (KCs) of the liver was detected. The isolated KCs were divided into control group, LPS group, TGF group and Galunisertib group and western blot analysis was used to detect the expression of NF-κB, IL-6, IL-1β, TNF-α, iNOS and Arg-1. The percentage of CD40, CD86, CD204 and CD206 as macrophage cell surface antigens were measured by flow cytometry. The indexes of liver function and liver fibrosis of the mice in the TGF group were significantly lower than those in the BDL group (P<0.05). The levels of IL-1β, IL-6 and TNF-α in the liver were lower than those in the BDL group, while the level of IL-10 was significantly increased (P<0.05). M2-type transformation occurred in liver Kupffer cells of mice in the TGF group. In cell experiments, TGF treatment downregulated the expression of IL-1β, IL-6, TNF-α and NF-κB, increased the expression of IL-10, and induced M2-type transformation in macrophages (P<0.05). In conclusion, TGF-ß1 diminished the progression of cholestasis in mice by inhibiting the inflammatory response of KCs and regulating KC polarization.