원문정보
초록
영어
Microglial activation is one of the prominent features of neurodegeneration. Activated microglia may lead to the induction of proinflammatory cytokines and nitric oxide (NO), key regulatory molecules that are stimulating neuronal damage. Therefore, inhibiting microglial activation may have therapeutic benefits for neurodegenerative diseases. In this study, we evaluated the ability of the natural peroxisome proliferator-activated receptor γ (PPARγ) ligands and agonist to modulate microglial activation in response to inflammogens such as lipopolysaccharide (LPS) and heat-inactivated Staphylococcus aureus (S. aureus). The prostaglandin D2 (PGD2) metabolites, 12-PGJ2 and 15d-PGJ2 significantly suppressed NO production by LPS in microglia. 15d-PGJ2 also selectively inhibited the S. aureus-dependent increase in microglial NO generation. Interestingly, PPARγ agonist pioglitazone (1 uM) prevented the LPS- and S.
aureus-induced NO production. These findings suggest that prostaglandin metabolite 15d-PGJ2 and PPARγ agonist pioglitazone effectively repress microglial production of potentially cytotoxic molecules.