c-Jun N-Terminal Kinase 1 Is Required for Toll-Like Receptor 1 Gene Expression in Macrophages

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c-Jun N-Terminal Kinase 1 Is Required for Toll-Like Receptor 1 Gene Expression in Macrophages

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Title: c-Jun N-Terminal Kinase 1 Is Required for Toll-Like Receptor 1 Gene Expression in Macrophages
Author: Izadi, Hooman;Motameni, Amirreza T.;Bates, Tonya C.;Olivera, Elias R.;Villar-Suárez, V.;Joshi, Ila;Garg, Renu;Osborne, Barbara A.;Davis, Roger J.;Rincón, Mercedes;Anguita, Juan
xmlui.dri2xhtml.METS-1.0.item-contributor: Facultad de Ciencias Biologicas y Ambientales
xmlui.dri2xhtml.METS-1.0.item-area: Bioquimica y Biologia Molecular
Abstract: The regulation of innate immune responses to pathogens occurs through the interaction of Toll-like receptors (TLRs) with pathogen-associated molecular patterns and the activation of several signaling pathways whose contribution to the overall innate immune response to pathogens is poorly understood. We demonstrate a mechanism of control of murine macrophage responses mediated by TLR1/2 heterodimers through c-Jun N-terminal kinase 1 (JNK1) activity. JNK controls tumor necrosis factor alpha production and TLR-mediated macrophage responses to Borrelia burgdorferi, the causative agent of Lyme disease, and the TLR1/TLR2-specific agonist PAM3CSK4. JNK1, but not JNK2, activity regulates the expression of the tlr1 gene in the macrophage cell line RAW264.7, as well as in primary CD11b cells. We also show that the proximal promoter region of the human tlr1 gene contains an AP-1 binding site that is subjected to regulation by the kinase and binds two complexes that involve the JNK substrates c-Jun, JunD, and ATF-2. These results demonstrate that JNK1 regulates the response to TLR1/2 ligands and suggest a positive feedback loop that may serve to increase the innate immune response to the spirochete
xmlui.dri2xhtml.METS-1.0.item-desfisica: P. 5027-5034
xmlui.dri2xhtml.METS-1.0.item-peerreviewed: SI
Publisher: American Society for Microbiology
xmlui.dri2xhtml.METS-1.0.item-citation: Infection and Immunity, 2007 (octubre)
URI: http://hdl.handle.net/10612/6448
Date: 2007-04-23
xmlui.dri2xhtml.METS-1.0.item-tipo: info:eu-repo/semantics/article
Subject: Bioquímica
xmlui.dri2xhtml.METS-1.0.item-palclave: Microbiología
Inmunología
Toll-like receptors (TLRs)
Macrophages
N-terminal kinase 1 (JNK1)
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