Microglia and Astrocyte Activation by Toll-Like Receptor Ligands: Modulation by PPAR-γ Agonists
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 exacerbat...
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| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2008-01-01
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| Series: | PPAR Research |
| Online Access: | http://dx.doi.org/10.1155/2008/453120 |
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| _version_ | 1849304827120582656 |
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| author | Catherine Gurley Jessica Nichols Shuliang Liu Nirmal K. Phulwani Nilufer Esen Tammy Kielian |
| author_facet | Catherine Gurley Jessica Nichols Shuliang Liu Nirmal K. Phulwani Nilufer Esen Tammy Kielian |
| author_sort | Catherine Gurley |
| collection | DOAJ |
| description | 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-γ 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-γ agonists to modulate glial activation. For example, 15d-PGJ2 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-PGJ2, 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. |
| format | Article |
| id | doaj-art-3cddde33530c4ff48d53a976a10247c8 |
| institution | Kabale University |
| issn | 1687-4757 1687-4765 |
| language | English |
| publishDate | 2008-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | PPAR Research |
| spelling | doaj-art-3cddde33530c4ff48d53a976a10247c82025-08-20T03:55:39ZengWileyPPAR Research1687-47571687-47652008-01-01200810.1155/2008/453120453120Microglia and Astrocyte Activation by Toll-Like Receptor Ligands: Modulation by PPAR-γ AgonistsCatherine Gurley0Jessica Nichols1Shuliang Liu2Nirmal K. Phulwani3Nilufer Esen4Tammy Kielian5Department of Neurobiology and Developmental Sciences, College of Medicine, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USADepartment of Neurobiology and Developmental Sciences, College of Medicine, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USADepartment of Neurobiology and Developmental Sciences, College of Medicine, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USADepartment of Neurobiology and Developmental Sciences, College of Medicine, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USADepartment of Neurobiology and Developmental Sciences, College of Medicine, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USADepartment of Neurobiology and Developmental Sciences, College of Medicine, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USAMicroglia 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-γ 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-γ agonists to modulate glial activation. For example, 15d-PGJ2 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-PGJ2, 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.http://dx.doi.org/10.1155/2008/453120 |
| spellingShingle | Catherine Gurley Jessica Nichols Shuliang Liu Nirmal K. Phulwani Nilufer Esen Tammy Kielian Microglia and Astrocyte Activation by Toll-Like Receptor Ligands: Modulation by PPAR-γ Agonists PPAR Research |
| title | Microglia and Astrocyte Activation by Toll-Like Receptor Ligands: Modulation by PPAR-γ Agonists |
| title_full | Microglia and Astrocyte Activation by Toll-Like Receptor Ligands: Modulation by PPAR-γ Agonists |
| title_fullStr | Microglia and Astrocyte Activation by Toll-Like Receptor Ligands: Modulation by PPAR-γ Agonists |
| title_full_unstemmed | Microglia and Astrocyte Activation by Toll-Like Receptor Ligands: Modulation by PPAR-γ Agonists |
| title_short | Microglia and Astrocyte Activation by Toll-Like Receptor Ligands: Modulation by PPAR-γ Agonists |
| title_sort | microglia and astrocyte activation by toll like receptor ligands modulation by ppar γ agonists |
| url | http://dx.doi.org/10.1155/2008/453120 |
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