deficiency of interleukin-15 enhances susceptibility to acetaminophen-induced liver injury in mice缺乏interleukin-15增强敏感性在对乙酰氨基酚诱导性肝损伤小鼠.pdfVIP

Deficiency of Interleukin-15 Enhances Susceptibility to Acetaminophen-Induced Liver Injury in Mice 1 1,2 1,2 1,3 4 Hsein-San Hou , Ching-Len Liao , Huey-Kang Sytwu , Nan-Shih Liao , Tien-Yu Huang , Tsai- Yuan Hsieh4, Heng-Cheng Chu1,4* 1 Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan, 2 Department of Microbiology and Immunology, National Defense Medical Center, Taipei, Taiwan, 3 Institute of Molecular Biology, Academia Sinica, Taipei, Taiwan, 4 Division of Gastroenterology and Hepatology, Department of Internal Medicine, Tri- Service General Hospital, National Defense Medical Center, Taipei, Taiwan Abstract Hepatocytes have a direct necrotic role in acetaminophen (APAP)-induced liver injury (AILI), prolonged secondary inflammatory response through innate immune cells and cytokines also significantly contributes to APAP hepatotoxicity. Interleukin 15 (IL-15), a multifunction cytokine, regulates the adaptive immune system and influences development and function of innate immune cells. To better understand the role of IL-15 in liver injury, we treated wild-type (WT) and IL-15- knockout (Il152/ 2) mice with a hepatotoxic dose of APAP to induce AILI and evaluated animal survival, liver damage, APAP metabolism in livers and the inflammatory response. Production of pro-inflammatory cytokines/chemokines was greater in Il152/ 2 than WT mice. Subanalysis of hepatic infiltrated monocytes revealed greater neutrophil influx, along with greater hepatic induction of inducible nitric oxide synthase (iNOS), in Il152/ 2 than WT mice. In addition, the level of hepatic hemeoxygenase 1 (HO-1) was partially suppressed in Il152/ 2 mice,