| First Author | Vila-del Sol V | Year | 2007 |
| Journal | J Leukoc Biol | Volume | 81 |
| Issue | 1 | Pages | 272-83 |
| PubMed ID | 17035338 | Mgi Jnum | J:117247 |
| Mgi Id | MGI:3695858 | Doi | 10.1189/jlb.0905529 |
| Citation | Vila-del Sol V, et al. (2007) Requirement of tumor necrosis factor alpha and nuclear factor-kappaB in the induction by IFN-gamma of inducible nitric oxide synthase in macrophages. J Leukoc Biol 81(1):272-83 |
| abstractText | IFN-gamma induces NO production, inducible NO synthase (iNOS) protein, and promoter expression in mouse macrophage cells. Mutation of IFN regulatory factor 1 responsive element, gamma-activated site, as well as NF-kappaB elements in the murine iNOS promoter strongly reduced IFN-gamma-induced iNOS transcriptional activity. The role of NF-kappaB activation in iNOS induction by IFN-gamma was corroborated by overexpression of the NF-kappaB inhibitory protein IkappaBalpha, which inhibited iNOS promoter activity induced by IFN-gamma. In addition, IFN-gamma treatment induced p65 binding to the iNOS promoter by chromatin immunoprecipitation assay and NF-kappaB binding to DNA by EMSA, although with a delayed kinetics, suggesting an indirect autocrine role for another cytokine produced in response to IFN-gamma. It is interesting that we found that IFN-gamma induced TNF-alpha secretion, and the induction of iNOS expression by IFN-gamma was abolished in primary peritoneal macrophages from TNF-alpha-deficient (TNF-alpha-/-) mice or in RAW 264.7 cells treated with anti-TNF-alpha neutralizing antibodies. Moreover, exogenous addition of recombinant mouse TNF-alpha restored iNOS expression induced by IFN-gamma in TNF-alpha-/- mice. It is intriguing that NF-kappaB binding to DNA in response to IFN-gamma treatment was absent in TNF-alpha-/- mice. Taken together, our data suggest that the TNF-alpha produced in response to IFN-gamma is required for iNOS induction by activating NF-kappaB transcription factor. |
