Toll-like receptor - Mediated cytokine production is differentially regulated by glycogen synthase kinase 3

Michael Martin, Kunal Rehani, Richard S Jope, Suzanne M. Michalek

Research output: Contribution to journalArticle

734 Citations (Scopus)

Abstract

The cellular mechanisms that directly regulate the inflammatory response after Toll-like receptor (TLR) stimulation are unresolved at present. Here we report that glycogen synthase kinase 3 (GSK3) differentially regulates TLR-mediated production of pro- and anti-inflammatory cytokines. Stimulation of monocytes or peripheral blood mononuclear cells with TLR2, TLR4, TLR5 or TLR9 agonists induced substantial increases in interleukin 10 production while suppressing the release of proinflammatory cytokines after GSK3 inhibition. GSK3 regulated the inflammatory response by differentially affecting the nuclear amounts of transcription factors NF-κB subunit p65 and CREB interacting with the coactivator CBP. Administration of a GSK3 inhibitor potently suppressed the proinflammatory response in mice receiving lipopolysaccharide and mediated protection from endotoxin shock. These findings demonstrate a regulatory function for GSK3 in modulating the inflammatory response.

Original languageEnglish
Pages (from-to)777-784
Number of pages8
JournalNature Immunology
Volume6
Issue number8
DOIs
StatePublished - Aug 1 2005
Externally publishedYes

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Glycogen Synthase Kinase 3
Toll-Like Receptors
Cytokines
Endotoxins
Interleukin-10
Lipopolysaccharides
Monocytes
Shock
Blood Cells
Anti-Inflammatory Agents
Transcription Factors

ASJC Scopus subject areas

  • Immunology

Cite this

Toll-like receptor - Mediated cytokine production is differentially regulated by glycogen synthase kinase 3. / Martin, Michael; Rehani, Kunal; Jope, Richard S; Michalek, Suzanne M.

In: Nature Immunology, Vol. 6, No. 8, 01.08.2005, p. 777-784.

Research output: Contribution to journalArticle

Martin, Michael ; Rehani, Kunal ; Jope, Richard S ; Michalek, Suzanne M. / Toll-like receptor - Mediated cytokine production is differentially regulated by glycogen synthase kinase 3. In: Nature Immunology. 2005 ; Vol. 6, No. 8. pp. 777-784.
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