ALA (α-lipoic acid) is a natural, endogenous antioxidant that acts as a PPAR-γ (peroxisome-proliferator-activated receptor-γ) agonist to counteract oxidative stress. Thus far, the antioxidative and immunomodulatory effects of ALA on EAE (experimental autoimmune encephalomyelitis) are not well understood. In this study, we found that ALA restricts the infiltration of inflammatory cells into the CNS (central nervous system) in MOG (myelin oligodendrocyte glycoprotein)-EAE mice, thus reducing the disease severity. In addition, we revealed that ALA significantly suppresses the number and percentage of encephalitogenic Th1 and Th17 cells and increases splenic Treg-cells (regulatory T-cells). Strikingly, we further demonstrated that ALA induces endogenous PPAR-γ centrally and peripherally but has no effect on HO-1 (haem oxygenase 1). Together, these data suggest that ALA can up-regulate endogenous systemic and central PPAR-γ and enhance systemic Treg-cells 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 immunomodulatory mechanisms for the application of ALA in human MS (multiple sclerosis).
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Research Article|
June 07 2013
α-Lipoic acid enhances endogenous peroxisome-proliferator-activated receptor-γ to ameliorate experimental autoimmune encephalomyelitis in mice
Kai-Chen Wang;
Kai-Chen Wang
*Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, Taiwan
†Cheng Hsin General Hospital, Taipei, Taiwan
‡School of Medicine, National Yang-Ming University, Taipei, Taiwan
§Neurological Institute, Taipei Veterans General Hospital, Taipei, Taiwan
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Ching-Piao Tsai;
Ching-Piao Tsai
1
†Cheng Hsin General Hospital, Taipei, Taiwan
§Neurological Institute, Taipei Veterans General Hospital, Taipei, Taiwan
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Chao-Lin Lee;
Chao-Lin Lee
1
§Neurological Institute, Taipei Veterans General Hospital, Taipei, Taiwan
∥Department of Neurology, I-Lan Hospital, I-Lan, Taiwan
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Shao-Yuan Chen;
Shao-Yuan Chen
¶School of Medicine, Fu-Jen Catholic University, Taipei, Taiwan
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Gu-Jiun Lin;
Gu-Jiun Lin
**Department of Biology and Anatomy, National Defense Medical Center, Taipei, Taiwan
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Mao-Hsiung Yen;
Mao-Hsiung Yen
1
††Department of Pharmacology, National Defense Medical Center, Taipei, Taiwan
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Huey-Kang Sytwu;
Huey-Kang Sytwu
1
*Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, Taiwan
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Shyi-Jou Chen
*Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, Taiwan
‡‡Department of Pediatrics, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
Correspondence: Dr Shyi-Jou Chen (email [email protected]).
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Publisher: Portland Press Ltd
Received:
October 15 2012
Revision Received:
April 01 2013
Accepted:
April 03 2013
Accepted Manuscript online:
April 03 2013
Online ISSN: 1470-8736
Print ISSN: 0143-5221
© The Authors Journal compilation © 2013 Biochemical Society
2013
Clin Sci (Lond) (2013) 125 (7): 329–340.
Article history
Received:
October 15 2012
Revision Received:
April 01 2013
Accepted:
April 03 2013
Accepted Manuscript online:
April 03 2013
Citation
Kai-Chen Wang, Ching-Piao Tsai, Chao-Lin Lee, Shao-Yuan Chen, Gu-Jiun Lin, Mao-Hsiung Yen, Huey-Kang Sytwu, Shyi-Jou Chen; α-Lipoic acid enhances endogenous peroxisome-proliferator-activated receptor-γ to ameliorate experimental autoimmune encephalomyelitis in mice. Clin Sci (Lond) 1 October 2013; 125 (7): 329–340. doi: https://doi.org/10.1042/CS20120560
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