Peroxisome proliferator-activated receptor-gamma agonists inhibit the activation of microglia and astrocytes: Implications for multiple sclerosis

Abstract Peroxisome proliferator-activated receptor (PPAR)-γ agonists, including thiazolidinediones (TZDs) and 15-deoxy-Δ 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-α, IL-1β, 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-γ agonists modulate EAE, at least in part, by inhibiting the activation of microglia and astrocytes. The studies further suggest that PPAR-γ agonists may be effective in the treatment of MS.