IL-10 promotes survival of microglia without activating Akt

Klemen Strle; Jian Hua Zhou; Suzanne R. Broussard; Homer D. Venters; Rodney W. Johnson; Gregory G. Freund; Robert Dantzer; Keith W. Kelley

doi:10.1016/S0165-5728(01)00444-1

IL-10 promotes survival of microglia without activating Akt

Klemen Strle, Jian Hua Zhou, Suzanne R. Broussard, Homer D. Venters, Rodney W. Johnson, Gregory G. Freund, Robert Dantzer, Keith W. Kelley

Research output: Contribution to journal › Article › peer-review

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 Tyr⁷⁰⁵ 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 serine⁴⁷³ 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.

Original language	English (US)
Pages (from-to)	9-19
Number of pages	11
Journal	Journal of Neuroimmunology
Volume	122
Issue number	1-2
DOIs	https://doi.org/10.1016/S0165-5728(01)00444-1
State	Published - 2002

Keywords

Akt
Apoptosis
IGF-I
IL-10
Phosphatidylinositol 3′ -kinase
Stat3

ASJC Scopus subject areas

Immunology and Allergy
Immunology
Neurology
Clinical Neurology

Online availability

10.1016/S0165-5728(01)00444-1

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@article{47db611955df4850a8205526450514a6,

title = "IL-10 promotes survival of microglia without activating Akt",

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 Tyr705 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 serine473 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.",

keywords = "Akt, Apoptosis, IGF-I, IL-10, Phosphatidylinositol 3′ -kinase, Stat3",

author = "Klemen Strle and Zhou, {Jian Hua} and Broussard, {Suzanne R.} and Venters, {Homer D.} and Johnson, {Rodney W.} and Freund, {Gregory G.} and Robert Dantzer and Kelley, {Keith W.}",

note = "Funding Information: This research was supported by grants from the National Institutes of Health to K.W.K. (MH-51569) and R.W.J. (AG-16710), and by the Pioneering Research Project in Biotechnology financed by the Japanese Ministry of Agriculture, Forestry and Fisheries to K.W.K. ",

year = "2002",

doi = "10.1016/S0165-5728(01)00444-1",

language = "English (US)",

volume = "122",

pages = "9--19",

journal = "Journal of Neuroimmunology",

issn = "0165-5728",

publisher = "Elsevier B.V.",

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}

TY - JOUR

T1 - IL-10 promotes survival of microglia without activating Akt

AU - Strle, Klemen

AU - Zhou, Jian Hua

AU - Broussard, Suzanne R.

AU - Venters, Homer D.

AU - Johnson, Rodney W.

AU - Freund, Gregory G.

AU - Dantzer, Robert

AU - Kelley, Keith W.

N1 - Funding Information: This research was supported by grants from the National Institutes of Health to K.W.K. (MH-51569) and R.W.J. (AG-16710), and by the Pioneering Research Project in Biotechnology financed by the Japanese Ministry of Agriculture, Forestry and Fisheries to K.W.K.

PY - 2002

Y1 - 2002

N2 - 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 Tyr705 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 serine473 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.

AB - 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 Tyr705 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 serine473 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.

KW - Akt

KW - Apoptosis

KW - IGF-I

KW - IL-10

KW - Phosphatidylinositol 3′ -kinase

KW - Stat3

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U2 - 10.1016/S0165-5728(01)00444-1

DO - 10.1016/S0165-5728(01)00444-1

M3 - Article

C2 - 11777539

AN - SCOPUS:0036147475

SN - 0165-5728

VL - 122

SP - 9

EP - 19

JO - Journal of Neuroimmunology

JF - Journal of Neuroimmunology

IS - 1-2

ER -

IL-10 promotes survival of microglia without activating Akt

Abstract

Keywords

ASJC Scopus subject areas

Online availability

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