Curcumin reduces Ly6Chi monocyte infiltration to protect against liver fibrosis by inhibiting Kupffer cells activation to reduce chemokines secretion

Abstract

Curcumin has been reported to have anti-fibrotic effect. However, the anti-fibrotic mechanism of curcumin for liver fibrosis remains obscure. In the presenting study, we aimed to investigate whether curcumin reduce chemokines secretion by inhibiting kupffer cells (KCs) activation to decrease Ly6Chi monocyte infiltration in the treatment of liver fibrosis. Liver fibrosis was induced by intraperitoneal carbon tetrachloride (CCl4)-injection in mice. Mice in curcumin group received curcumin treatment by gavage. Pretreatment with curcumin significantly protected mice from liver inflammation and fibrosis. Compared to CCl4 group, mice in the curcumin group showed significantly less intrahepatic infiltration of Ly6Chi monocytes, but no difference of other leucocyte subtypes. Moreover, curcumin significantly reduced Ly6Chi monocytes associated pro-inflammatory and pro-fibrogenic cytokines, which was in line with the decreased numbers of intrahepatic Ly6Chi monocytes. Further study found that curcumin is able to decrease KCs activation and monocyte chemokines, which explains why curcumin can reduce Ly6Chi monocytes infiltration during liver fibrosis. In vitro, we discovered that curcumin prevents the polarization of macrophages toward M1 and reduces monocyte chemokines secretion, which is involved with ERK1/2 and p38 pathways. Taken together, for the first time, we verified that curcumin can reduce chemokines secretion by inhibiting KCs activation to decrease Ly6Chi monocyte infiltration in the treatment of liver fibrosis. These results suggested that curcumin may be considered a promising candidate in the prevention and treatment of liver fibrosis.