Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, Taiwan.
Clin Sci (Lond). 2013 Oct;125(7):329-40. doi: 10.1042/CS20120560.
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).
ALA（α-硫辛酸）是一种天然的内源性抗氧化剂，可作为 PPAR-γ（过氧化物酶体增殖物激活受体-γ）激动剂来抵抗氧化应激。到目前为止，ALA 对 EAE（实验性自身免疫性脑脊髓炎）的抗氧化和免疫调节作用还不是很清楚。在这项研究中，我们发现 ALA 限制了 MOG（髓鞘少突胶质细胞糖蛋白）-EAE 小鼠中炎性细胞浸润中枢神经系统（CNS），从而降低了疾病的严重程度。此外，我们还揭示了 ALA 显著抑制了致脑炎性 Th1 和 Th17 细胞的数量和百分比，并增加了脾脏 Treg 细胞（调节性 T 细胞）。值得注意的是，我们进一步证明 ALA 在中枢和外周诱导内源性 PPAR-γ，但对 HO-1（血红素加氧酶 1）没有影响。总之，这些数据表明，ALA 可以上调内源性系统性和中枢性 PPAR-γ，并增强系统性 Treg 细胞，以抑制炎症反应和改善 MOG-EAE。总之，我们的数据首次提供了证据表明，ALA 可以在体内增强 PPAR-γ 的产生，并在 EAE 中调节中枢和外周的适应性免疫，这可能为 ALA 在人类多发性硬化症（MS）中的应用揭示了进一步的抗氧化和免疫调节机制。
