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c-Jun N-terminal kinase 1 is required for Toll-like receptor 1 gene expression in macrophages
Authors
Izadi, HoomanMotameni, Amirreza T.
Bates, Tonya C.
Olivera, Elias R.
Villar-Suarez, Vega
Joshi, Ila
Garg, Renu
Osborne, Barbara A.
Davis, Roger J.
Rincon, Mercedes
Anguita, Juan
UMass Chan Affiliations
Program in Molecular MedicineDocument Type
Journal ArticlePublication Date
2007-10-01Keywords
innate immune responsesToll-like receptors (TLRs)
c-Jun N-terminal kinase 1 (JNK1)
Biochemistry
Cell Biology
Cellular and Molecular Physiology
Immunity
Immunology of Infectious Disease
Molecular Biology
Metadata
Show full item recordAbstract
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.Source
Infect Immun. 2007 Oct;75(10):5027-34. Epub 2007 Jul 30. Link to article on publisher's siteDOI
10.1128/IAI.00492-07Permanent Link to this Item
http://hdl.handle.net/20.500.14038/28330PubMed ID
17664270Related Resources
Link to Article in PubMedRights
Publisher PDF posted as allowed by the publisher's author rights policy at http://journals.asm.org/site/misc/ASM_Author_Statement.xhtml.ae974a485f413a2113503eed53cd6c53
10.1128/IAI.00492-07