Storer Paul D, Xu Jihong, Chavis Janet, Drew Paul D
Department of Neurobiology and Developmental Sciences, University of Arkansas for Medical Sciences, Slot 510, 4301 West Markham Street, Little Rock, AR 72205, USA.
J Neuroimmunol. 2005 Apr;161(1-2):113-22. doi: 10.1016/j.jneuroim.2004.12.015.
Peroxisome proliferator-activated receptor (PPAR)-gamma agonists, including thiazolidinediones (TZDs) and 15-deoxy-Delta(12,14) prostaglandin J(2) (15d-PGJ(2)), have been shown to be effective in the treatment of experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS). This study aimed to compare the anti-inflammatory actions of three TZDs - rosiglitazone, pioglitazone, and ciglitazone - with those of 15d-PGJ(2) on stimulated mouse microglia and astrocytes. The results show that TZDs and 15d-PGJ(2) are effective in inhibiting production of nitric oxide, the pro-inflammatory cytokines TNF-alpha, IL-1beta, and IL-6, and the chemokine MCP-1 from microglia and astrocytes. However, 15d-PGJ(2) was a more potent suppressor of pro-inflammatory activity than the TZDs. These studies suggest that PPAR-gamma agonists modulate EAE, at least in part, by inhibiting the activation of microglia and astrocytes. The studies further suggest that PPAR-gamma agonists may be effective in the treatment of MS.
过氧化物酶体增殖物激活受体（PPAR）-γ激动剂，包括噻唑烷二酮类（TZDs）和15-脱氧-Δ（12,14）前列腺素J2（15d-PGJ2），已被证明在治疗实验性自身免疫性脑脊髓炎（EAE）方面有效，EAE是多发性硬化症（MS）的一种动物模型。本研究旨在比较三种TZDs（罗格列酮、吡格列酮和环格列酮）与15d-PGJ2对刺激的小鼠小胶质细胞和星形胶质细胞的抗炎作用。结果表明，TZDs和15d-PGJ2在抑制小胶质细胞和星形胶质细胞产生一氧化氮、促炎细胞因子TNF-α、IL-1β和IL-6以及趋化因子MCP-1方面有效。然而，15d-PGJ2比TZDs更有效地抑制促炎活性。这些研究表明，PPAR-γ激动剂至少部分地通过抑制小胶质细胞和星形胶质细胞的激活来调节EAE。这些研究进一步表明，PPAR-γ激动剂可能对MS的治疗有效。
