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Astrocytes in injury states rapidly produce anti‐inflammatory factors and attenuate microglial inflammatory responses
Author(s) -
Kim Jonghyeon,
Min KyoungJin,
Seol Wongi,
Jou Ilo,
Joe Eunhye
Publication year - 2010
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2010.07004.x
Subject(s) - microglia , inflammatory response , inflammation , astrocyte , neuroscience , immunology , neuroinflammation , medicine , biology , central nervous system
J. Neurochem. (2010) 115 , 1161–1171. Abstract 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 5 min), 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 3 kDa, 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.