Alpha lipoic acid enhances endogenous peroxisome proliferator-activated receptor-γ to ameliorate experimental autoimmune encephalomyelitis

• Main Authors: Wang, Kai Chen, 王凱震
• Other Authors: Chen, Shyi-Jou
• Format: Others
• Language: en_US
• Published: 2013
• Online Access: http://ndltd.ncl.edu.tw/handle/99466047305944860673

博士 === 國防醫學院 === 醫學科學研究所 === 101 === Alpha lipoic acid (ALA) is a natural, endogenous antioxidant that acts as a peroxi-some proliferator-activated receptor-γ (PPAR-γ) agonist to counteract oxidative stress. Thus far, the antioxidative and immunomodulatory effects of ALA on experimental autoimmune encephalomyelitis (EAE) are not well understood. In this study, we found that ALA restricts the infiltration of inflammatory cells into the central nervous systems (CNS) in myelin oligodendrocyte glycoprotein (MOG)-EAE mice, thus re-ducing the disease severity. In addition, we revealed that ALA significantly suppress-es the number and percentage of encephalitogenic Th1 and Th17 cells and increases splenic regulatory T cells (Tregs). Strikingly, we further demonstrated that ALA in-duces endogenous PPAR-γ centrally and peripherally but has no effect on Heme oxy-genase 1. Together, these data suggest that ALA can upregulate endogenous systemic and central PPAR-γ and enhance systemic Tregs to inhibit the inflammatory response and ameliorate MOG-EAE. In conclusion, our data provide the first evidence that ALA can augment the production of PPAR-γ in vivo and modulate adaptive immunity both centrally and peripherally in EAE and may reveal further antioxidative and im-munomodulatory mechanisms for the application of ALA in human multiple sclerosis.