title: α-Lipoic acid enhances endogenous peroxisome-proliferator-activated receptor-γ to ameliorate experimental autoimmune encephalomyelitis in mice.
abstract: 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).
authors.affiliation: Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Kai-Chen
authors.initials: KC
authors.lastname: Wang
authors.forename: Ching-Piao
authors.initials: CP
authors.lastname: Tsai
authors.forename: Chao-Lin
authors.initials: CL
authors.lastname: Lee
authors.forename: Shao-Yuan
authors.initials: SY
authors.lastname: Chen
authors.forename: Gu-Jiun
authors.initials: GJ
authors.lastname: Lin
authors.forename: Mao-Hsiung
authors.initials: MH
authors.lastname: Yen
authors.forename: Huey-Kang
authors.initials: HK
authors.lastname: Sytwu
authors.forename: Shyi-Jou
authors.initials: SJ
authors.lastname: Chen
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use*; D004353:Drug Evaluation, Preclinical / Q000379:methods; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D051547:Heme Oxygenase-1 / Q000096:biosynthesis / Q000187:drug effects; D007166:Immunosuppressive Agents / Q000494:pharmacology / Q000627:therapeutic use; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D008565:Membrane Proteins / Q000096:biosynthesis / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D047495:PPAR gamma / Q000096:biosynthesis / Q000187:drug effects*; D013154:Spleen / Q000276:immunology / Q000637:transplantation; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology; D058504:Th17 Cells / Q000187:drug effects / Q000276:immunology; D008063:Thioctic Acid / Q000494:pharmacology / Q000627:therapeutic use*; D015854:Up-Regulation / Q000187:drug effects / Q000276:immunology
chemical_list: D000975:Antioxidants; D007166:Immunosuppressive Agents; D008565:Membrane Proteins; D047495:PPAR gamma; D008063:Thioctic Acid; D051547:Heme Oxygenase-1; C496542:Hmox1 protein, mouse