| First Author | Radwan M | Year | 2010 |
| Journal | J Immunol | Volume | 185 |
| Issue | 6 | Pages | 3544-53 |
| PubMed ID | 20713887 | Mgi Jnum | J:163818 |
| Mgi Id | MGI:4830007 | Doi | 10.4049/jimmunol.0904000 |
| Citation | Radwan M, et al. (2010) Tyrosine kinase 2 controls IL-1beta production at the translational level. J Immunol 185(6):3544-53 |
| abstractText | 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. |
