15-deoxy-?12,14-prostaglandin J2 (15d-PGJ2) and ciglitazone modulate Staphylococcus aureus-dependent astrocyte activation primarily through a PPAR-?-independent pathway
| Autor: | Nirmal K. Phulwani, Tammy Kielian, Candan Akar, Douglas L. Feinstein, Vitaliy Gavrilyuk |
|---|---|
| Rok vydání: | 2006 |
| Předmět: |
Staphylococcus aureus
medicine.medical_specialty Nitric Oxide Synthase Type II Peroxisome proliferator-activated receptor Biology Biochemistry Article Nitric oxide Mice Cellular and Molecular Neuroscience chemistry.chemical_compound Ciglitazone Internal medicine medicine Animals Hypoglycemic Agents Receptor Cells Cultured Mice Knockout chemistry.chemical_classification Prostaglandin D2 Toll-Like Receptor 2 Cell biology Mice Inbred C57BL PPAR gamma Nitric oxide synthase CXCL2 medicine.anatomical_structure Endocrinology Animals Newborn chemistry Astrocytes biology.protein Neuroglia Thiazolidinediones Inflammation Mediators Astrocyte |
| Zdroj: | Journal of Neurochemistry. 99:1389-1402 |
| ISSN: | 1471-4159 0022-3042 |
| DOI: | 10.1111/j.1471-4159.2006.04183.x |
| Popis: | Brain abscesses arise from a focal parenchymal infection by various pathogens, particularly Staphylococcus aureus. We have shown that astrocytes are activated upon exposure to S. aureus and may contribute to the excessive tissue damage characteristic of brain abscess. Therefore, modulating astrocyte activation may facilitate a reduction in brain abscess severity. Peroxisome proliferator activated receptor-gamma (PPAR-gamma) agonists are potent inhibitors of microglial activation; however, the effects of these compounds on S. aureus-dependent astrocyte activation have not yet been examined. Here, we demonstrate that two chemically distinct PPAR-gamma agonists, 15-deoxy-delta12,14-prostaglandin J2 (15d-PGJ2) and ciglitazone, suppress the production of several pro-inflammatory molecules in S. aureus-stimulated astrocytes including interleukin-1beta and nitric oxide (NO). Interestingly, 15d-PGJ2 attenuated Toll-like receptor 2 (TLR2) and inducible nitric oxide synthase expression, but failed to modulate macrophage inflammatory protein-2 (MIP-2/CXCL2) production, suggesting that 15d-PGJ2 is not a global inhibitor of astrocyte activation. Another novel finding of this study was the fact that both 15d-PGJ2 and ciglitazone were capable of attenuating pre-existing astrocyte activation, indicating their potential benefit in a therapeutic setting. Importantly, 15d-PGJ2 and ciglitazone were still capable of inhibiting S. aureus-induced pro-inflammatory mediator release in PPAR-gamma-deficient astrocytes, supporting PPAR-gamma-independent effects of these compounds. Collectively, these results suggest that 15d-PGJ2 and ciglitazone exert their anti-inflammatory actions on astrocytes primarily independent of the PPAR-gamma pathway. |
| Databáze: | OpenAIRE |
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