Published online before print October 11, 2006

This Article Full Text Full Text (PDF) All Versions of this Article: jlb.0905529v1 81/1/272    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Vila-del Sol, V. Articles by Fresno, M. Search for Related Content PubMed PubMed Citation Articles by Vila-del Sol, V. Articles by Fresno, M.

(Journal of Leukocyte Biology. 2007;81:272-283.)
© 2007 by Society for Leukocyte Biology

Requirement of tumor necrosis factor and nuclear factor-B in the induction by IFN- of inducible nitric oxide synthase in macrophages

Centro de Biología Molecular, Consejo Superior de Investigaciones Científicas-Universidad Autónoma de Madrid, Cantoblanco, Madrid, Spain

¹Correspondence: Centro de Biología Molecular, CSIC-UAM, Universidad Autónoma de Madrid, Cantoblanco, E-28049 Madrid, Spain. E-mail: mfresno{at}cbm.uam.es

IFN- induces NO production, inducible NO synthase (iNOS) protein, and promoter expression in mouse macrophage cells. Mutation of IFN regulatory factor 1 responsive element, -activated site, as well as NF-B elements in the murine iNOS promoter strongly reduced IFN--induced iNOS transcriptional activity. The role of NF-B activation in iNOS induction by IFN- was corroborated by overexpression of the NF-B inhibitory protein IB, which inhibited iNOS promoter activity induced by IFN-. In addition, IFN- treatment induced p65 binding to the iNOS promoter by chromatin immunoprecipitation assay and NF-B binding to DNA by EMSA, although with a delayed kinetics, suggesting an indirect autocrine role for another cytokine produced in response to IFN-. It is interesting that we found that IFN- induced TNF- secretion, and the induction of iNOS expression by IFN- was abolished in primary peritoneal macrophages from TNF--deficient (TNF-^–/–) mice or in RAW 264.7 cells treated with anti-TNF- neutralizing antibodies. Moreover, exogenous addition of recombinant mouse TNF- restored iNOS expression induced by IFN- in TNF-^–/– mice. It is intriguing that NF-B binding to DNA in response to IFN- treatment was absent in TNF-^–/– mice. Taken together, our data suggest that the TNF- produced in response to IFN- is required for iNOS induction by activating NF-B transcription factor.

Key Words: inflammation • monocytes • cytokine response • iNOS

This article has been cited by other articles:

				N. Rodriguez, R. Lang, N. Wantia, C. Cirl, T. Ertl, S. Durr, H. Wagner, and T. Miethke Induction of iNOS by Chlamydophila pneumoniae requires MyD88-dependent activation of JNK J. Leukoc. Biol., December 1, 2008; 84(6): 1585 - 1593. [Abstract] [Full Text] [PDF]

				V. Vila-del Sol, C. Punzon, and M. Fresno IFN-{gamma}-Induced TNF-{alpha} Expression Is Regulated by Interferon Regulatory Factors 1 and 8 in Mouse Macrophages J. Immunol., October 1, 2008; 181(7): 4461 - 4470. [Abstract] [Full Text] [PDF]

				N. K. Phulwani, N. Esen, M. Md. Syed, and T. Kielian TLR2 Expression in Astrocytes Is Induced by TNF-{alpha}- and NF-{kappa}B-Dependent Pathways J. Immunol., September 15, 2008; 181(6): 3841 - 3849. [Abstract] [Full Text] [PDF]

				D. T. Berg, A. Gupta, M. A. Richardson, L. A. O'Brien, D. Calnek, and B. W. Grinnell Negative Regulation of Inducible Nitric-oxide Synthase Expression Mediated through Transforming Growth Factor- -dependent Modulation of Transcription Factor TCF11 J. Biol. Chem., December 21, 2007; 282(51): 36837 - 36844. [Abstract] [Full Text] [PDF]

				K. P. Crume, J. H. Miller, and A. C. La Flamme Peloruside A, an Antimitotic Agent, Specifically Decreases Tumor Necrosis Factor-{alpha} Production by Lipopolysaccharide-Stimulated Murine Macrophages Experimental Biology and Medicine, May 1, 2007; 232(5): 607 - 613. [Abstract] [Full Text] [PDF]