c-Jun N-terminal kinase 1 is required for Toll-like receptor 1 gene expression in macrophages.

Titlec-Jun N-terminal kinase 1 is required for Toll-like receptor 1 gene expression in macrophages.
Publication TypeJournal Article
Year of Publication2007
AuthorsIzadi H, Motameni AT, Bates TC, Olivera ER, Villar-Suarez V, Joshi I, Garg R, Osborne BA, Davis RJ, Rincón M, Anguita J
JournalInfection and immunity
Volume75
Issue10
Pagination5027-34
Date Published2007 Oct
ISSN0019-9567
KeywordsAnimals, Base Sequence, Binding Sites, Borrelia burgdorferi, Cell Line, Cells, Cultured, Gene Expression Regulation, Humans, Macrophages, Mice, Mice, Inbred C57BL, Mitogen-Activated Protein Kinase 8, Molecular Sequence Data, Promoter Regions, Genetic, Toll-Like Receptor 1
AbstractThe 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 PAM(3)CSK(4). 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.
DOI10.1128/IAI.00492-07
Alternate JournalInfect. Immun.
PubMed ID17664270