This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Morris, K. R.
Right arrow Articles by Chan, E. D.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Morris, K. R.
Right arrow Articles by Chan, E. D.

 Previous Article  |  Next Article 

Infection and Immunity, March 2003, p. 1442-1452, Vol. 71, No. 3
0019-9567/03/$08.00+0     DOI: 10.1128/IAI.71.3.1442-1452.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Role of the NF-{kappa}B Signaling Pathway and {kappa}B cis-Regulatory Elements on the IRF-1 and iNOS Promoter Regions in Mycobacterial Lipoarabinomannan Induction of Nitric Oxide

Kristin R. Morris,1 Ryan D. Lutz,1 Hyung-Seok Choi,1 Tetsu Kamitani,2 Kathryn Chmura,1 and Edward D. Chan1,3,4,5*

Department of Medicine,1 Program in Cell Biology, National Jewish MedicalResearch Center,3 Division of Pulmonary Sciences and Critical Care Medicine, University of Colorado Health Sciences Center,4 Denver Veterans Administration Medical Center, Denver, Colorado,5 Division of Molecular Medicine, University of Texas-Houston Health Science Center, Houston, Texas 770302

Received 2 August 2002/ Returned for modification 12 September 2002/ Accepted 31 October 2002

Nitric oxide (NO·) produced by inducible nitric oxide synthase (iNOS) is an important host defense molecule against Mycobacterium tuberculosis in mononuclear phagocytes. The objective of this study was to determine the role of the I{kappa}B{alpha} kinase-nuclear factor {kappa}B (IKK-NF-{kappa}B) signaling pathway in the induction of iNOS and NO· by a mycobacterial cell wall lipoglycan known as mannose-capped lipoarabinomannan (ManLAM) in mouse macrophages costimulated with gamma interferon (IFN-{gamma}). NF-{kappa}B was activated by ManLAM as shown by electrophoretic mobility shift assay, by immunofluorescence of translocated NF-{kappa}B in intact cells, and by a reporter gene driven by four NF-{kappa}B-binding elements. Transduction of an I{kappa}B{alpha} mutant (Ser32/36Ala) significantly inhibited NO· expression induced by IFN-{gamma} plus ManLAM. An activated SCF complex, a heterotetramer (Skp1, Cul-1, ß-TrCP [F-box protein], and ROC1) involved with ubiquitination, is also required for iNOS-NO· induction. Two NF-{kappa}B-binding sites ({kappa}BI and {kappa}BII) present on the 5'-flanking region of the iNOS promoter bound ManLAM-induced NF-{kappa}B similarly. By use of reporter constructs in which one or both sites are mutated, both NF-{kappa}B-binding positions were essential in iNOS induction by IFN-{gamma} plus ManLAM. IFN-{gamma}-induced activation of the IRF-1 transcriptional complex is a necessary component in host defense against tuberculosis. Although the 5'-flanking region of the IRF-1 promoter contains an NF-{kappa}B-binding site and ManLAM-induced NF-{kappa}B also binds to this site, ManLAM was unable to induce IRF-1 expression. The influence of mitogen-activated protein kinases on IFN-{gamma} plus ManLAM induction of iNOS-NO· is not due to any effects on ManLAM induction of NF-{kappa}B.

* Corresponding author. Mailing address: K613e, Goodman Building, National Jewish Medical and Research Center, 1400 Jackson St., Denver, CO 80206. Phone: (303) 398-1491. Fax: (303) 398-1806. E-mail: chane{at}njc.org.

Editor: J. T. Barbieri

Infection and Immunity, March 2003, p. 1442-1452, Vol. 71, No. 3
0019-9567/03/$08.00+0     DOI: 10.1128/IAI.71.3.1442-1452.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Chmura, K., Bai, X., Nakamura, M., Kandasamy, P., McGibney, M., Kuronuma, K., Mitsuzawa, H., Voelker, D. R., Chan, E. D. (2008). Induction of IL-8 by Mycoplasma pneumoniae membrane in BEAS-2B cells. Am. J. Physiol. Lung Cell. Mol. Physiol. 295: L220-L230 [Abstract] [Full Text]  
  • Collier-Hyams, L. S., Sloane, V., Batten, B. C., Neish, A. S. (2005). Cutting Edge: Bacterial Modulation of Epithelial Signaling via Changes in Neddylation of Cullin-1. J. Immunol. 175: 4194-4198 [Abstract] [Full Text]  
  • Takada, Y., Kobayashi, Y., Aggarwal, B. B. (2005). Evodiamine Abolishes Constitutive and Inducible NF-{kappa}B Activation by Inhibiting I{kappa}B{alpha} Kinase Activation, Thereby Suppressing NF-{kappa}B-regulated Antiapoptotic and Metastatic Gene Expression, Up-regulating Apoptosis, and Inhibiting Invasion. J. Biol. Chem. 280: 17203-17212 [Abstract] [Full Text]  
  • Takada, Y., Aggarwal, B. B. (2004). Evidence that genetic deletion of the TNF receptor p60 or p80 in macrophages modulates RANKL-induced signaling. Blood 104: 4113-4121 [Abstract] [Full Text]  
  • Hestvik, A. L. K., Hmama, Z., Av-Gay, Y. (2003). Kinome Analysis of Host Response to Mycobacterial Infection: a Novel Technique in Proteomics. Infect. Immun. 71: 5514-5522 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»