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 Lee, S.-B.
Right arrow Articles by Schorey, J. S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Lee, S.-B.
Right arrow Articles by Schorey, J. S.

 Previous Article  |  Next Article 

Infection and Immunity, October 2005, p. 6499-6507, Vol. 73, No. 10
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.10.6499-6507.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Activation and Mitogen-Activated Protein Kinase Regulation of Transcription Factors Ets and NF-{kappa}B in Mycobacterium-Infected Macrophages and Role of These Factors in Tumor Necrosis Factor Alpha and Nitric Oxide Synthase 2 Promoter Function

Seong-Beom Lee{dagger} and Jeffrey S. Schorey*

Department of Biological Sciences, Center for Tropical Disease Research and Training, University of Notre Dame, Notre Dame, Indiana 46556

Received 8 April 2005/ Returned for modification 23 May 2005/ Accepted 17 June 2005

Previous studies have shown that primary murine macrophages infected with Mycobacterium avium produced lower levels of tumor necrosis factor alpha (TNF-{alpha}) and inducible nitric oxide synthase 2 (NOS2) compared to cells infected with nonpathogenic Mycobacterium smegmatis. TNF-{alpha} and NOS2 levels correlated with and were dependent on the activation of mitogen-activated protein kinases (MAPKs) p38 and extracellular signal-regulated kinase 1/2 (ERK1/2). To define the macrophage transcriptional responses dependent on ERK1/2 activation following a mycobacterial infection, we used RAW 264.7 cells transfected with a TNF-{alpha} or NOS2 promoter vector. We determined that macrophages infected with M. avium compared to M. smegmatis showed diminished TNF-{alpha} and NOS2 promoter activity. A more pronounced difference in promoter activity was observed when only the consensus ETS and NF-{kappa}B binding sites were used as promoters. Mutational analysis of the ETS and NF-{kappa}B binding sites present on the TNF-{alpha} and NOS2 promoters, respectively, showed that these sites were essential for a functional promoter. Moreover, the Ets/Elk but not the NF-{kappa}B transcriptional response was dependent on ERK1/2. This correlated with the requirement for ERK1/2 in TNF-{alpha} but not NOS2 promoter activity. Our data indicate that the increased Ets/Elk and NF-{kappa}B promoter activities associated with M. smegmatis-infected macrophages are responsible, at least in part, for the increased TNF-{alpha} and NOS2 production observed in these infected cells and that ERK1/2 is required for Ets/Elk activity and full TNF-{alpha} production.

* Corresponding author. Mailing address: Department of Biology, University of Notre Dame, 130 Galvin Life Science Center, Notre Dame, IN 46556. Phone: (574) 631-3734. Fax: (574) 631-7413. E-mail: schorey.1{at}nd.edu.

Editor: W. A. Petri, Jr.

{dagger} Present address: Institute of Hansen's Disease, College of Medicine, The Catholic University of Korea, 505-Manpo-dong, Socho-gu, Seoul, 137-701 Korea.

Infection and Immunity, October 2005, p. 6499-6507, Vol. 73, No. 10
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.10.6499-6507.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Han, M., Yan, W., Guo, W., Xi, D., Zhou, Y., Li, W., Gao, S., Liu, M., Levy, G., Luo, X., Ning, Q. (2008). Hepatitis B Virus-induced hFGL2 Transcription Is Dependent on c-Ets-2 and MAPK Signal Pathway. J. Biol. Chem. 283: 32715-32729 [Abstract] [Full Text]  
  • Sampaio, E. P., Elloumi, H. Z., Zelazny, A., Ding, L., Paulson, M. L., Sher, A., Bafica, A. L., Shea, Y. R., Holland, S. M. (2008). Mycobacterium abscessus and M. avium Trigger Toll-Like Receptor 2 and Distinct Cytokine Response in Human Cells. Am. J. Respir. Cell Mol. Bio. 39: 431-439 [Abstract] [Full Text]  
  • Gutierrez, M. G., Mishra, B. B., Jordao, L., Elliott, E., Anes, E., Griffiths, G. (2008). NF-{kappa}B Activation Controls Phagolysosome Fusion-Mediated Killing of Mycobacteria by Macrophages. J. Immunol. 181: 2651-2663 [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»