IL-10 promotes survival of microglia without activating Akt.
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.
Strle
Klemen
K
Laboratory of Immunophysiology, Department of Animal Sciences, University of Illinois, 207 ERML, 1201 W. Gregory Dr., Urbana, IL 61801, USA.
Zhou
Jian Hua
JH
Broussard
Suzanne R
SR
Venters
Homer D
HD
Johnson
Rodney W
RW
Freund
Gregory G
GG
Dantzer
Robert
R
Kelley
Keith W
KW
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002455:Cell Division; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004396:Coloring Agents; D004268:DNA-Binding Proteins / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D016753:Interleukin-10 / Q000494:pharmacology*; D051379:Mice; D017628:Microglia / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt; D017526:Receptor, IGF Type 1 / Q000096:biosynthesis; D018123:Receptors, Interleukin / Q000096:biosynthesis; D053701:Receptors, Interleukin-10; D050796:STAT3 Transcription Factor; D012694:Serine / Q000378:metabolism; D013778:Tetrazolium Salts; D013844:Thiazoles; D015534:Trans-Activators / Q000378:metabolism; D014443:Tyrosine / Q000378:metabolism
D004396:Coloring Agents; D004268:DNA-Binding Proteins; D007334:Insulin-Like Growth Factor I; D016753:Interleukin-10; D019869:Phosphatidylinositol 3-Kinases; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt; D017526:Receptor, IGF Type 1; D018123:Receptors, Interleukin; D053701:Receptors, Interleukin-10; D050796:STAT3 Transcription Factor; D012694:Serine; D013778:Tetrazolium Salts; D013844:Thiazoles; D015534:Trans-Activators; D014443:Tyrosine; C494087:Stat3 protein, mouse; C022616:thiazolyl blue