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

Storer, Paul D., Xu, Jihong, Chavis, Janet, Drew, Paul D.·2005·Journal of Neuroimmunology
DOI 10.1016/j.jneuroim.2004.12.015
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Abstract

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.

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  • PPARγ is a ligand-modulated transcription factor which, through heterodimers with RXR, regulates expression of genes involved in lipid and glucose metabolism; it also exerts a neuroprotective and anti-inflammatory role in the CNS.

    “PPARγ is a ligand-modulated transcription factor which, through the formation of heterodimers with the retinoid X receptor (RXR), regulates the expression of genes involved in lipid and glucose metabolism [52]; in addition, it is known to exert a neuroprotective and anti-inflammatory role in the CNS [77,78].”

    From ApoE3 vs. ApoE4 Astrocytes: A Detailed Analysis Provides New Insights into Differences in Cholesterol Homeostasis (2022) · cites this paper as [77]

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Metadata

Authors
Storer, P. D., Xu, J., Chavis, J., & Drew, P. D.
Venue
Journal of Neuroimmunology
Publisher
Elsevier BV
Published
2005-04
Volume
161
Issue
1-2
Pages
113-122
ISSN
0165-5728
DOI
10.1016/j.jneuroim.2004.12.015
Cited by
154
References
1
Language
en
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