Hepatoprotective Role of Endogenous Interleukin-13 in a Murine Model of Acetaminophen-Induced Liver Disease
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- 作者：Steven B. Yee ; Mohammed Bourdi ; Mary Jane Masson ; Lance R. Pohl
- 刊名：Chemical Research in Toxicology
- 出版年：2007
- 出版时间：May 2007
- 年：2007
- 卷：20
- 期：5
- 页码：734 - 744
- 全文大小：1185K
- 年卷期：v.20,no.5(May 2007)
- ISSN：1520-5010
文摘
Recent evidence suggests that a deficiency in one or more hepatoprotective regulatory mechanismsmay contribute to determining susceptibility in drug-induced liver disease. In the present study, weinvestigated the role of interleukin (IL)-13 in acetaminophen (APAP)-induced liver disease (AILD).Following APAP (200 mg/kg) administration to male C57BL/6 wild-type (WT) mice, hepatotoxicitydeveloped up to 24 h post-APAP, with a concomitant increase in serum IL-13 concentration. Pretreatmentof these mice with an IL-13-neutralizing antibody exacerbated liver injury, as did APAP administrationto IL-13 knockout (KO) mice in comparison to WT mice. No difference was observed in either overallAPAP-protein adduct formation or liver glutathione levels between KO and WT mice following APAPadministration, suggesting that the increased susceptibility of IL-13 KO mice to AILD was not due toenhanced APAP bioactivation but rather injurious downstream events. In this regard, multiplex antibodyarrays were used to identify potential IL-13-regulated biomarkers, including various cytokines andchemokines, as well as nitric oxide (NO), associated with AILD that were present at higher concentrationsin the sera of APAP-treated IL-13 KO mice than in WT mice. Subsequent inhibition studies determinedinterferon-
rs/gamma.gif" BORDER=0 >, NO, neutrophils, natural killer cells, and natural killer cells with T-cell receptors hadpathologic roles in AILD in IL-13 KO mice. Taken together, these results suggest that IL-13 is a criticalhepatoprotective factor modulating the susceptibility to AILD and may provide hepatoprotection, in part,by down-regulating protoxicant factors and cells associated with the innate immune system.
rs/gamma.gif" BORDER=0 >, NO, neutrophils, natural killer cells, and natural killer cells with T-cell receptors hadpathologic roles in AILD in IL-13 KO mice. Taken together, these results suggest that IL-13 is a criticalhepatoprotective factor modulating the susceptibility to AILD and may provide hepatoprotection, in part,by down-regulating protoxicant factors and cells associated with the innate immune system.