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Tyrosine kinase 2 controls IL-1ß production at the translational level.

ABSTRACT: IL-1beta is an important proinflammatory cytokine with a major role in several inflammatory diseases. Expression of IL-1beta is tightly regulated at the level of transcription, mRNA stability, and proteolytic processing. In this study, we report that IL-1beta expression in response to LPS is also regulated at the translational level. LPS-induced IL-1beta protein levels in macrophages derived from murine bone marrow are markedly increased in the absence of tyrosine kinase 2 (Tyk2). Increased IL-1beta is found intra- and extracellularly, irrespective of the efficiency of IL-1beta processing. We show that the absence of Tyk2 results both in higher translational rates and in enhanced association of IL-1beta mRNA with polysomes. Induction and stability of IL-1beta mRNA are not affected by the lack of Tyk2. We show further that the Tyk2-dependent translational inhibition is mediated by autocrine/paracrine type I IFN signaling and requires signal transducer and activator of transcription 1. Enhanced IL-1beta production in Tyk2- and IFN receptor 1-deficient macrophages is also observed following Listeria monocytogenes infection. Taken together, the data describe a novel mechanism for the control of IL-1beta synthesis.

SUBMITTER: Radwan M

PROVIDER: S-EPMC2990881 | biostudies-literature | 2010 Sep

REPOSITORIES: biostudies-literature

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Tyrosine kinase 2 controls IL-1ß production at the translational level.

Radwan Marta M Stiefvater Rita R Grunert Tom T Sharif Omar O Miller Ingrid I Marchetti-Deschmann Martina M Allmaier Günter G Gemeiner Manfred M Knapp Sylvia S Kovarik Pavel P Müller Mathias M Strobl Birgit B

Journal of immunology (Baltimore, Md. : 1950) 20100816 6

IL-1beta is an important proinflammatory cytokine with a major role in several inflammatory diseases. Expression of IL-1beta is tightly regulated at the level of transcription, mRNA stability, and proteolytic processing. In this study, we report that IL-1beta expression in response to LPS is also regulated at the translational level. LPS-induced IL-1beta protein levels in macrophages derived from murine bone marrow are markedly increased in the absence of tyrosine kinase 2 (Tyk2). Increased IL-1 ...[more]

PMID: 20713887

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Tyrosine kinase 2 controls IL-1ß production at the translational level.

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Tyrosine kinase 2 controls IL-1ß production at the translational level.

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