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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Apoptosis / drug effects
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Cell Division
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Cell Survival / drug effects
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Cells, Cultured
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Coloring Agents
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DNA-Binding Proteins / metabolism
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Enzyme Activation / drug effects
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Insulin-Like Growth Factor I / pharmacology
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Interleukin-10 / pharmacology*
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Mice
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Microglia / cytology*
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Microglia / drug effects
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Microglia / metabolism
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Phosphatidylinositol 3-Kinases / metabolism
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Phosphorylation
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Protein Serine-Threonine Kinases*
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Proto-Oncogene Proteins / metabolism*
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Proto-Oncogene Proteins c-akt
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Receptor, IGF Type 1 / biosynthesis
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Receptors, Interleukin / biosynthesis
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Receptors, Interleukin-10
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STAT3 Transcription Factor
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Serine / metabolism
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Tetrazolium Salts
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Thiazoles
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Trans-Activators / metabolism
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Tyrosine / metabolism
Substances
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Coloring Agents
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DNA-Binding Proteins
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Proto-Oncogene Proteins
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Receptors, Interleukin
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Receptors, Interleukin-10
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STAT3 Transcription Factor
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Stat3 protein, mouse
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Tetrazolium Salts
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Thiazoles
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Trans-Activators
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Interleukin-10
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Tyrosine
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Serine
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Insulin-Like Growth Factor I
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Receptor, IGF Type 1
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Protein Serine-Threonine Kinases
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Proto-Oncogene Proteins c-akt
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thiazolyl blue