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PPAR Research
Volume 2008 (2008), Article ID 453120, 15 pages
http://dx.doi.org/10.1155/2008/453120
Research Article

Microglia and Astrocyte Activation by Toll-Like Receptor Ligands: Modulation by PPAR- Agonists

Department of Neurobiology and Developmental Sciences, College of Medicine, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA

Received 10 March 2008; Accepted 5 May 2008

Academic Editor: Michael Racke

Copyright © 2008 Catherine Gurley et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Microglia and astrocytes express numerous members of the Toll-like receptor (TLR) family that are pivotal for recognizing conserved microbial motifs expressed by a wide array of pathogens. Despite the critical role for TLRs in pathogen recognition, when dysregulated these pathways can also exacerbate CNS tissue destruction. Therefore, a critical balance must be achieved to elicit sufficient immunity to combat CNS infectious insults and down-regulate these responses to avoid pathological tissue damage. We performed a comprehensive survey on the efficacy of various PPAR- agonists to modulate proinflammatory mediator release from primary microglia and astrocytes in response to numerous TLR ligands relevant to CNS infectious diseases. The results demonstrated differential abilities of select PPAR- agonists to modulate glial activation. For example, 15d-PG and pioglitazone were both effective at reducing IL-12 p40 release by TLR ligand-activated glia, whereas CXCL2 expression was either augmented or inhibited by 15d-PG , effects that were dependent on the TLR ligand examined. Pioglitazone and troglitazone demonstrated opposing actions on microglial CCL2 production that were TLR ligand-dependent. Collectively, this information may be exploited to modulate the host immune response during CNS infections to maximize host immunity while minimizing inappropriate bystander tissue damage that is often characteristic of such diseases.