Mechanisms of bile acid–induced (BA-induced) liver injury in cholestasis are controversial, limiting development of new therapies. We examined how BAs initiate liver injury using isolated liver cells from humans and mice and in-vivo mouse models. At pathophysiologic concentrations, BAs induced proinflammatory cytokine expression in mouse and human hepatocytes, but not in nonparenchymal cells or cholangiocytes. These hepatocyte-specific cytokines stimulated neutrophil chemotaxis. Inflammatory injury was mitigated in
Shi-Ying Cai, Xinshou Ouyang, Yonglin Chen, Carol J. Soroka, Juxian Wang, Albert Mennone, Yucheng Wang, Wajahat Z. Mehal, Dhanpat Jain, James L. Boyer
Tlr9 is involved in bile acid induction of Cxcl2 in vitro in mouse hepatocytes and in vivo in BDL mouse liver.