Journal
JOURNAL OF NEUROIMMUNOLOGY
Volume 161, Issue 1-2, Pages 113-122Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.jneuroim.2004.12.015
Keywords
PPAR; thiazolidinedione; 15d-PGJ(2); glia; cytokine; chemokine
Categories
Funding
- NINDS NIH HHS [P30 NS047546-01A1, NS042860, R01 NS042860, NS047546, R01 NS042860-03, P30 NS047546] Funding Source: Medline
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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-1 beta, 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. (C) 2005 Elsevier B.V All rights reserved.
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