Phosphoinositide 3-kinase-gamma expression is upregulated in brain microglia and contributes to ischemia-induced microglial activation in acute experimental stroke.
Microglia, the resident microphages of the CNS, are rapidly activated after ischemic stroke. Inhibition of microglial activation may protect the brain by attenuating blood-brain barrier damage and neuronal apoptosis after ischemic stroke. However, the mechanisms by which microglia is activated following cerebral ischemia is not well defined. In this study, we investigated the expression of PI3Kgamma in normal and ischemic brains and found that PI3Kgamma mRNA and protein are constitutively expressed in normal brain microvessels, but significantly upregulated in postischemic brain primarily in activated microglia following cerebral ischemia. In vitro, the expression of PI3Kgamma mRNA and protein was verified in mouse brain endothelial and microglial cell lines. Importantly, absence of PI3Kgamma blocked the early microglia activation (at 4h) and subsequent expansion (at 24-72 h) in PI3Kgamma knockout mice. The results suggest that PI3Kgamma is an ischemia-responsive gene in brain microglia and contributes to ischemia-induced microglial activation and expansion.
Jin
Rong
R
Department of Neurosurgery, Vascular Biology & Stroke Research Laboratory, Louisiana State University Health Sciences Center, Shreveport, LA, USA.
Yu
Shiyong
S
Song
Zifang
Z
Quillin
Joseph W
JW
Deasis
Daniel P
DP
Penninger
Josef M
JM
Nanda
Anil
A
Granger
D Neil
DN
Li
Guohong
G
D000818:Animals; D001921:Brain / Q000098:blood supply / Q000201:enzymology*; D002545:Brain Ischemia / Q000201:enzymology*; D002196:Capillaries / Q000201:enzymology; D058544:Class Ib Phosphatidylinositol 3-Kinase; D007527:Isoenzymes / Q000096:biosynthesis / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000201:enzymology*; D019869:Phosphatidylinositol 3-Kinases / Q000096:biosynthesis* / Q000235:genetics; D020521:Stroke / Q000201:enzymology*
D007527:Isoenzymes; D019869:Phosphatidylinositol 3-Kinases; D058544:Class Ib Phosphatidylinositol 3-Kinase; C546764:Pik3cg protein, mouse