RT Journal Article SR Electronic T1 Heme Oxygenase-1 Alleviates Mouse Hepatic Failure through Suppression of Adaptive Immune Responses JF Journal of Pharmacology and Experimental Therapeutics JO J Pharmacol Exp Ther FD American Society for Pharmacology and Experimental Therapeutics SP 2 OP 10 DO 10.1124/jpet.111.186551 VO 340 IS 1 A1 Qiaoli Gu A1 Qiong Wu A1 Min Jin A1 Yichuan Xiao A1 Jingwei Xu A1 Chaoming Mao A1 Fang Zhao A1 Yi Zhang A1 Yanyun Zhang YR 2012 UL http://jpet.aspetjournals.org/content/340/1/2.abstract AB Heme oxygenase-1 (HO-1) has protective effects on liver damage induced by noxious stimuli. The mechanism of action of HO-1 is not well understood. In the present study, we investigate the effect of HO-1 in a model of fulminant hepatic failure induced by Propionibacterium acnes and lipopolysaccharide (LPS). The expression of HO-1 mRNA and protein in the liver was increased after repeated administration of the HO-1 inducer cobalt protoporphyrin IX. We found that HO-1 protected mice from acute liver damage induced by P. acnes/LPS and prolonged survival. On the contrary, administration of the HO-1 inhibitor zinc protoporphyrin IX increased liver damage induced by P. acnes/LPS. Subsequently, to investigate the underlying mechanisms of HO-1 in the acute liver injury model, we primed mice with P. acnes only. We found that the expression of HO-1 mRNA and protein in dendritic cells (DCs) was increased after the administration of cobalt protoporphyrin IX. HO-1 decreased the mature markers major histocompatibility complex II and CD80 on liver DCs. The expression of CCR7, CCL2, and CCL22 mRNA, which are expressed by mature DCs, was also reduced. These liver DCs could not efficiently stimulate CD4+ T cell activation and proliferation. Consequently, HO-1 inhibited the activation, proliferation, and T helper 1 polarization of liver-infiltrating CD4+ T cells and reduced the production of serum alanine aminotransferase and proinflammatory cytokines such as interferon-γ and tumor necrosis factor-α. Taken together, our data suggest that HO-1 alleviates P. acnes/LPS-induced fulminant hepatic failure, probably by inhibiting DC-induced adaptive responses.