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Astrocytes in injury states rapidly produce anti-inflammatory factors and attenuate microglial inflammatory responses.

Kim, JH; Min, KJ; Seol, W; Jou, I; Joe, EH
Journal of neurochemistry, 115(5):1161-1171, 2010
Journal Title
Journal of neurochemistry
Microglia are known to be a primary inflammatory cell type in the brain. However, microglial inflammatory responses are attenuated in the injured brain compared to those in cultured pure microglia. In the present study, we found that astrocytes challenged by oxygen-glucose deprivation (OGD) or H(2) O(2) released soluble factor(s) and attenuated microglial inflammatory responses. Conditioned medium prepared from astrocytes treated with OGD (OGD-ACM) or H(2) O(2) (H(2) O(2) -ACM) significantly reduced the levels of interferon-γ (IFN-γ)-induced microglial inflammatory mediators, including inducible nitric oxide synthase, at both the mRNA and protein levels. The anti-inflammatory effect of astrocytes appeared very rapidly (within 5min), but was not closely correlated with the extent of astrocyte damage. Both OGD-ACM and H(2) O(2) -ACM inhibited STAT nuclear signaling, as evidenced by a reduction in both STAT-1/3 binding to the IFN-γ-activated site and IFN-γ-activated site promoter activity. However, both phosphorylation and nuclear translocation of STAT-1/3 was unchanged in IFN-γ-treated microglia. The active component(s) in OGD-ACM were smaller than 3kDa, and displayed anti-inflammatory effects independent of protein synthesis. These results suggest that, in the injured brain, astrocytes may act as a controller to rapidly suppress microglial activation.
MeSH terms
AnimalsAnimals, NewbornAnoxia/metabolismAnti-Inflammatory Agents/pharmacology*Astrocytes/chemistryAstrocytes/drug effectsAstrocytes/physiology*Cerebral Cortex/cytologyCulture Media, Conditioned/pharmacologyElectrophoretic Mobility Shift Assay/methodsGene Expression Regulation/drug effectsGene Expression Regulation/physiology*Glucose/deficiencyHydrogen Peroxide/pharmacologyInterferon-gamma/pharmacologyIntracellular Fluid/drug effectsIntracellular Fluid/metabolismL-Lactate Dehydrogenase/metabolismMicroglia/drug effects*Nitric Oxide Synthase Type II/metabolismOligonucleotides/metabolismRNA, Messenger/metabolismRatsRats, Sprague-DawleyReactive Oxygen Species/metabolismSTAT Transcription Factors/metabolismTransfection/methods
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Pharmacology
AJOU Authors
주, 일로조, 은혜
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