Author | Hines, Ian N. | |
Author | Kremer, Michael | |
Author | Moore, Sherri M. | |
Author | Wheeler, Michael D. | |
Date Accessioned | 2018-07-02T16:15:24Z | |
Date Available | 2018-07-02T16:15:24Z | |
Date of Issue | 2018-02-15 | |
Identifier (Citation) | Hines, I. N., Kremer, M., Moore, S. M., & Wheeler, M. D. (2018). Impaired T cell-mediated hepatitis in peroxisome proliferator activated receptor alpha (PPARα)-deficient mice. Biological Research, 51(1), 5. https://doi.org/10.1186/s40659-018-0153-z | en_US |
Identifier (URI) | http://hdl.handle.net/10342/6811 | |
Description | Copyright
© The Author(s) 2018. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License, (http://creativecommons.org/licenses/by/4.0/).
The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/
publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. | en_US |
Description | 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. | en_US |
Sponsorship | ECU Open Access Publishing Support Fund | en_US |
Language | en_US | en_US |
Related URI | https://biolres.biomedcentral.com/articles/10.1186/s40659-018-0153-z | en_US |
Subject | Inflammation | en_US |
Subject | Cytokines | en_US |
Subject | T helper phenotype | en_US |
Subject | Interferon gamma | en_US |
Title | Impaired T cell-mediated hepatitis in peroxisome proliferator activated receptor alpha (PPARα)-deficient mice | en_US |
Type | Article | en_US |
Identifier (DOI) | https://doi.org/10.1186/s40659-018-0153-z | |
Journal Name | Biological Research | en_US |
Journal Volume | 51 | en_US |
Journal Issue | 5 | en_US |
Article Pages | 1-16 | en_US |