查看文章

Inflammation contributes to liver injury during cholestasis. The mechanism by which cholestasis initiates an inflammatory response in the liver, however, is not known. Two hypotheses were investigated in the present studies. First, activation of Toll-like receptor 4 (TLR4), either by bacterial lipopolysaccharide or by damage-associated molecular pattern molecules released from dead hepatocytes, triggers an inflammatory response. Second, bile acids act as inflammagens, and directly activate signaling pathways in hepatocytes that stimulate production of proinflammatory mediators. Liver inflammation was not affected in lipopolysaccharide-resistant C3H/HeJ mice after bile duct ligation, indicating that Toll-like receptor 4 is not required for initiation of inflammation. Treatment of hepatocytes with bile acids did not directly cause cell toxicity but increased the expression of numerous proinflammatory mediators, including …