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

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Animals, Newborn
  • Astrocytes / drug effects*
  • Astrocytes / physiology
  • Blotting, Western / methods
  • Cell Survival / drug effects
  • Cells, Cultured
  • Cerebral Cortex / cytology
  • Chemokines / metabolism
  • Cytokines / metabolism
  • Cytokines / pharmacology
  • Dose-Response Relationship, Drug
  • Drug Interactions
  • Enzyme-Linked Immunosorbent Assay / methods
  • Gene Expression Regulation / drug effects*
  • Inhibitory Concentration 50
  • Lipopolysaccharides / pharmacology
  • Mice
  • Microglia / drug effects*
  • Microglia / physiology
  • Nitric Oxide / metabolism
  • PPAR gamma / agonists*
  • Prostaglandin D2 / analogs & derivatives*
  • Prostaglandin D2 / pharmacology*
  • Thiazolidinediones / pharmacology*


  • 15-deoxy-delta(12,14)-prostaglandin J2
  • Chemokines
  • Cytokines
  • Lipopolysaccharides
  • PPAR gamma
  • Thiazolidinediones
  • Nitric Oxide
  • Prostaglandin D2