| First Author | Izadi H | Year | 2007 |
| Journal | Infect Immun | Volume | 75 |
| Issue | 10 | Pages | 5027-34 |
| PubMed ID | 17664270 | Mgi Jnum | J:125281 |
| Mgi Id | MGI:3758123 | Doi | 10.1128/IAI.00492-07 |
| Citation | Izadi H, et al. (2007) c-Jun N-terminal kinase 1 is required for Toll-like receptor 1 gene expression in macrophages. Infect Immun 75(10):5027-34 |
| abstractText | 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 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. |
