Astrocytes down-regulate microglial inflammatory responses

Microglia, the major inflammatory cells in the brain, are activated in injured brain and produce several inflammatory mediators. Previously, it has been reported that soluble factors from cultured astrocytes are capable of suppressing microglial activation. However, brain injury affect not only microglia but astrocytes. Therefore, I examined how astrocytes in injury states modulate microglial activation. Astrocytes were treated with oxygen-glucose deprivation (OGD) or hydrogen peroxide (H₂O₂, 0.01-1 mM), and culture conditioned media (OGDACM or H₂O₂-ACM) were collected. Both OGD-ACM and H₂O₂-ACM collected within 3 h after the treatment strongly reduced iNOS, COX-2, TNF-alpha, and IL-6 in interferon-γ (IFN-γ)-activated microglia. However, OGD-ACM collected from dead astrocytes at 24 h after the treatment did not reduce IFN-γ-induced iNOS expression. OGD-ACM inhibited microglial activation via direct suppression of IFN-γ-signaling without protein synthesis such as HO-1 or SOCS. The target regulated by OGD-ACM appeared to be in the nucleus since OGD-ACM did not inhibit phosphorylation and translocation from the cytosol to the nucleus of STAT 1/3 but reduced GAS-promoter activity. Taken together, these results suggest that astrocytes in injured brain suppress microglial activation to prevent severe inflammation and inflammation-induced secondary damage.

Author dc:creator

• 김, 종현

Contributors dc:contributor

• 조, 은혜
• 대학원 의학과
• 200624311

• astrocyte
• microglia
• 염증반응

Language dc:language

en

Identifier

http://dcoll.ajou.ac.kr:9080/dcollection/jsp/common/DcLoOrgPer.jsp?sItemId=000000009348
000000009348

OAI identifier oai:identifier

oai:repository.ajou.ac.kr:201003/1357