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Biological Research

versión impresa ISSN 0716-9760

Resumen

HINES, Ian N.; KREMER, Michael; MOORE, Sherri M.  y  WHEELER, Michael D.. Impaired T cell-mediated hepatitis in peroxisome proliferator activated receptor alpha (PPARα)-deficient mice. Biol. Res. [online]. 2018, vol.51, 5.  Epub 08-Mar-2018. ISSN 0716-9760.  http://dx.doi.org/10.1186/s40659-018-0153-z.

Background

Peroxisome proliferator activated receptor alpha (PPARα), a regulator of enzymes involved in β oxidation, has been reported to influence lymphocyte activation. The purpose of this study was to determine whether PPARα plays a role in T cell-mediated hepatitis induced by Concanavalin A (ConA).

Methods

Wild type (wt) or PPARα-deficient (PPARα−/−) 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 (IFNγ). In contrast, PPARα−/− mice were protected from ConA-induced liver injury with significant reductions in serum enzyme release, greatly reduced inflammatory cell infiltrate, hepatocellular apoptosis, and IFNγ 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 PPARα−/− splenocytes reconstituted ConA liver injury and cytokine production in lymphocyte-deficient, severe combined immunodeficient mice implicating PPARα 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 PPARα within the liver plays an important role in ConA-mediated liver injury through regulation of NKT cell recruitment and/or survival.

Palabras clave : Inflammation; Cytokines; T helper phenotype; Interferon gamma.

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