IL-10 directly protects cortical neurons by activating PI-3 kinase and STAT-3 pathways.
IL-10 reduces pro-inflammatory responses after ischemic stroke primarily by acting on glia and endothelium, but relatively little is known about the direct effects of IL-10 on cortical neurons, which are often damaged in stroke. We found by PCR and immunohistochemistry that cortical neurons express IL-10 receptor. Treatment of primary cortical neurons in culture with IL-10 increased neuronal survival after exposure to oxygen-glucose deprivation (OGD) or glutamate toxicity. IL-10 also induced phosphorylation of AKT in cortical neurons. Pretreatment with the specific PI-3K inhibitor, wortmannin, attenuated IL-10 mediated neuroprotection against OGD and glutamate. In addition, IL-10 induced STAT-3 phosphorylation. Pre-treatment with a functional blocking antibody to the IL-10 receptor reduced both Stat-3 and AKT phosphorylation and blocked IL-10 mediated protection of cortical neurons. These data suggest that IL-10 provides neuroprotection by acting via IL-10 receptor and PI3K/AKT and STAT-3 signal transduction pathways.
Department of Neurology, Stroke Program, University of Texas Medical School at Houston, Houston, TX 77030, USA.
Sushil
S
Sharma
Bing
B
Yang
Xiaopei
X
Xi
James C
JC
Grotta
Jaroslaw
J
Aronowski
Sean I
SI
Savitz
D000704:Analysis of Variance; D000818:Animals; D016923:Cell Death / Q000187:drug effects; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004622:Embryo, Mammalian; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D005947:Glucose / Q000172:deficiency; D018698:Glutamic Acid / Q000633:toxicity; D000860:Hypoxia; D016753:Interleukin-10 / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects*; D009498:Neurotoxins / Q000633:toxicity; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D053724:Receptors, Interleukin-18 / Q000235:genetics / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D013778:Tetrazolium Salts; D013844:Thiazoles; D014443:Tyrosine / Q000378:metabolism
D004791:Enzyme Inhibitors; D009498:Neurotoxins; D012333:RNA, Messenger; D053724:Receptors, Interleukin-18; D050796:STAT3 Transcription Factor; C494088:Stat3 protein, rat; D013778:Tetrazolium Salts; D013844:Thiazoles; D016753:Interleukin-10; D018698:Glutamic Acid; D014443:Tyrosine; D019869:Phosphatidylinositol 3-Kinases; C022616:thiazolyl blue; D005947:Glucose