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IL-10 promotes survival of microglia without activating Akt.
Authors:Klemen Strle  Jian Hua Zhou  Suzanne R Broussard  Homer D Venters  Rodney W Johnson  Gregory G Freund  Robert Dantzer  Keith W Kelley
Affiliation:Laboratory of Immunophysiology, Department of Animal Sciences, University of Illinois, 207 ERML, 1201 W. Gregory Dr., Urbana, IL 61801, USA.
Abstract:IL-10 is an anti-inflammatory cytokine that has recently been shown to promote survival of neurons and glia. Here we establish that IL-10 induces phosphorylation of Stat3 on Tyr(705) and serves as a survival factor for N13 microglial cells. Recombinant IL-10 (10 ng/ml) decreases growth factor withdrawal-induced apoptosis by 50%, as assessed by TUNEL. In contrast to IL-10, IGF-I increases enzymatic activity of PI 3-kinase and causes phosphorylation on serine(473) of Akt but does not prevent microglial apoptosis. These data establish that IL-10 activates Stat3 and inhibits the mitochondrial pathway of cell death without activating the Akt cell survival pathway.
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