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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<jats:italic>Borrelia burgdorferi<\/jats:italic>, the causative agent of Lyme disease, and the TLR1\/TLR2-specific agonist PAM<jats:sub>3<\/jats:sub>CSK<jats:sub>4<\/jats:sub>. JNK1, but not JNK2, activity regulates the expression of the<jats:italic>tlr1<\/jats:italic>gene in the macrophage cell line RAW264.7, as well as in primary CD11b<jats:sup>+<\/jats:sup>cells. We also show that the proximal promoter region of the human<jats:italic>tlr1<\/jats:italic>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.<\/jats:p>","DOI":"10.1128\/iai.00492-07","type":"journal-article","created":{"date-parts":[[2007,7,31]],"date-time":"2007-07-31T00:59:11Z","timestamp":1185843551000},"page":"5027-5034","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":17,"title":["c-Jun N-Terminal Kinase 1 Is Required for Toll-Like Receptor 1 Gene Expression in Macrophages"],"prefix":"10.1128","volume":"75","author":[{"given":"Hooman","family":"Izadi","sequence":"first","affiliation":[{"name":"Department of Veterinary and Animal Sciences, University of Massachusetts Amherst, Amherst, Massachusetts 01003"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amirreza T.","family":"Motameni","sequence":"additional","affiliation":[{"name":"Department of 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