Impaired T cell-mediated hepatitis in peroxisome proliferator activated receptor alpha (PPAR?)-deficient mice

ECU Author/Contributor (non-ECU co-authors, if there are any, appear on document)
Ian N. Hines (Creator)
Michael Kremer (Creator)
Sherri M. Moore (Creator)
Michael D. Wheeler (Creator)
Institution
East Carolina University (ECU )
Web Site: http://www.ecu.edu/lib/

Abstract: Abstract Background Peroxisome proliferator activated receptor alpha (PPAR?) , a regulator of enzymes involved in ß oxidation , has been reported to influence lymphocyte activation. The purpose of this study was to determine whether PPAR? plays a role in T cell-mediated hepatitis induced by Concanavalin A (ConA). Methods Wild type (wt) or PPAR?-deficient (PPAR?ˆ’/ˆ’) mice were treated with ConA (15 mg/kg) by intravenous injection 0 , 10 or 24 h prior to sacrifice and serum and tissue collection for analysis of tissue injury , cytokine response , T cell activation and characterization. Results Ten and 24 h following ConA administration , wt mice had significant liver injury as demonstrated by serum transaminase levels , inflammatory cell infiltrate , hepatocyte apoptosis , and expression of several cytokines including interleukin 4 (IL4) and interferon gamma (IFNy). In contrast , PPAR?ˆ’/ˆ’ mice were protected from ConA-induced liver injury with significant reductions in serum enzyme release , greatly reduced inflammatory cell infiltrate , hepatocellular apoptosis , and IFNy expression , despite having similar levels of hepatic T cell activation and IL4 expression. This resistance to liver injury was correlated with reduced numbers of hepatic natural killer T (NKT) cells and their in vivo responsiveness to alpha-galactosylceramide. Interestingly , adoptive transfer of either wt or PPAR?ˆ’/ˆ’ splenocytes reconstituted ConA liver injury and cytokine production in lymphocyte-deficient , severe combined immunodeficient mice implicating PPAR? within the liver , possibly through support of IL15 expression and/or suppression of IL12 production and not the lymphocyte as the key regulator of T cell activity and ConA-induced liver injury. Conclusion Taken together , these data suggest that PPAR? within the liver plays an important role in ConA-mediated liver injury through regulation of NKT cell recruitment and/or survival.

Additional Information

Publication
Other
Biological Research. 2018 Feb 15;51(1):5
Language: English
Date: 2018
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Impaired T cell-mediated hepatitis in peroxisome proliferator activated receptor alpha (PPAR?)-deficient micehttp://hdl.handle.net/10342/6566The described resource references, cites, or otherwise points to the related resource.