Impaired T cell-mediated hepatitis in peroxisome proliferator activated receptor alpha (PPARα)-deficient mice
Biol. Res
;
51: 5, 2018. tab, graf
Article
in English
| LILACS
| ID: biblio-888430
ABSTRACT
Abstract 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.
Full text:
Available
Index:
LILACS (Americas)
Main subject:
T-Lymphocytes
/
Cytokines
/
Macrolides
/
Hepatitis, Autoimmune
/
PPAR alpha
/
Galactosylceramides
Limits:
Animals
Language:
English
Journal:
Biol. Res
Journal subject:
Biology
Year:
2018
Type:
Article
/
Project document
Affiliation country:
United States
Institution/Affiliation country:
East Carolina University/US
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