RT info:eu-repo/semantics/article T1 c-Jun N-Terminal Kinase 1 Is Required for Toll-Like Receptor 1 Gene Expression in Macrophages A1 Izadi, Hooman A1 Motameni, Amirreza T. A1 Bates, Tonya C. A1 Olivera, Elias R. A1 Villar Suárez, María Vega A1 Joshi, Ila A1 Garg, Renu A1 Osborne, Barbara A. A1 Davis, Roger J. A1 Rincón, Mercedes A1 Anguita, Juan A2 Bioquimica y Biologia Molecular K1 Bioquímica K1 Microbiología K1 Inmunología K1 Toll-like receptors (TLRs) K1 Macrophages K1 N-terminal kinase 1 (JNK1) AB 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 pathwayswhose contribution to the overall innate immune response to pathogens is poorly understood. We demonstratea mechanism of control of murine macrophage responses mediated by TLR1/2 heterodimers through c-JunN-terminal kinase 1 (JNK1) activity. JNK controls tumor necrosis factor alpha production and TLR-mediatedmacrophage responses to Borrelia burgdorferi, the causative agent of Lyme disease, and the TLR1/TLR2-specificagonist PAM3CSK4. JNK1, but not JNK2, activity regulates the expression of the tlr1 gene in the macrophagecell line RAW264.7, as well as in primary CD11b cells. We also show that the proximal promoter region ofthe human tlr1 gene contains an AP-1 binding site that is subjected to regulation by the kinase and binds twocomplexes that involve the JNK substrates c-Jun, JunD, and ATF-2. These results demonstrate that JNK1regulates the response to TLR1/2 ligands and suggest a positive feedback loop that may serve to increase theinnate immune response to the spirochete PB American Society for Microbiology YR 2017 FD 2017-07-19 LK http://hdl.handle.net/10612/6448 UL http://hdl.handle.net/10612/6448 NO Infection and Immunity, 2007 (octubre) NO P. 5027-5034 DS BULERIA. Repositorio Institucional de la Universidad de León RD 28-mar-2024