| First Author | Hou HS | Year | 2012 |
| Journal | PLoS One | Volume | 7 |
| Issue | 9 | Pages | e44880 |
| PubMed ID | 23028657 | Mgi Jnum | J:191792 |
| Mgi Id | MGI:5463134 | Doi | 10.1371/journal.pone.0044880 |
| Citation | Hou HS, et al. (2012) Deficiency of interleukin-15 enhances susceptibility to acetaminophen-induced liver injury in mice. PLoS One 7(9):e44880 |
| abstractText | 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 (Il15(-)/(-)) 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 Il15(-)/(-) than WT mice. Subanalysis of hepatic infiltrated monocytes revealed greater neutrophil influx, along with greater hepatic induction of inducible nitric oxide synthase (iNOS), in Il15(-)/(-) than WT mice. In addition, the level of hepatic hemeoxygenase 1 (HO-1) was partially suppressed in Il15(-)/(-) mice, but not in WT mice. Interestingly, elimination of Kupffer cells and neutrophils did not alter the vulnerability to excess APAP in Il15(-)/(-) mice. However, injection of galactosamine, a hepatic transcription inhibitor, significantly reduced the increased APAP sensitivity in Il15(-)/(-) mice but had minor effect on WT mice. We demonstrated that deficiency of IL-15 increased mouse susceptibility to AILI. Moreover, Kupffer cell might affect APAP hepatotoxicity through IL-15. |
