Astrocytes, but not microglia, rapidly sense H₂O₂via STAT6 phosphorylation, resulting in cyclooxygenase-2 expression and prostaglandin release.

Emerging evidence has established that astrocytes, once considered passive supporting cells that maintained extracellular ion levels and served as a component of the blood-brain barrier, play active regulatory roles during neurogenesis and in brain pathology. In the current study, we demonstrated that astrocytes sense H(2)O(2) by rapidly phosphorylating the transcription factor a response not observed in microglia. phosphorylation was induced by generators of other reactive oxygen species and reactive nitrogen species, as well as in the reoxygenation phase of hypoxia/reoxygenation, during which are generated. Src-JAK pathways mediated duanyu18136 phosphorylation upstream. Experiments using lipid raft disruptors and analyses of detergent-fractionated cells demonstrated that H(2)O(2)-induced duanyu18136 phosphorylation occurred in lipid rafts. Under experimental conditions in which H(2)O(2) did not affect astrocyte viability, H(2)O(2)-induced duanyu18136 phosphorylation resulted in cyclooxygenase-2 expression and subsequent release of PGE(2) and prostacyclin, an effect also observed in hypoxia/reoxygenation. Finally, PGs released from H(2)O(2)-stimulated astrocytes inhibited microglial TNF-α expression. Accordingly, our results indicate that duanyu18136 phosphorylation in astrocytes can modulate the functions of neighboring cells, including microglia, through cyclooxygenase-2 induction and subsequent release of PGs. Differences in the sensitivity of duanyu18136 in astrocytes (highly sensitive) and microglia (insensitive) to phosphorylation following brief exposure to H(2)O(2) suggest that astrocytes can act as sentinels for certain stimuli, including H(2)O(2) and refining the canonical notion that microglia are the first line of defense against external stimuli.

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