HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 279, Issue 53, 55127-55136, December 31, 2004

This Article Full Text Full Text (PDF) All Versions of this Article: 279/53/55127    most recent M409885200v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend 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 Pathak, S. K. Articles by Basu, J. Search for Related Content PubMed PubMed Citation Articles by Pathak, S. K. Articles by Basu, J. Social Bookmarking                      What's this?

Toll-like Receptor 2 and Mitogen- and Stress-activated Kinase 1 Are Effectors of Mycobacterium avium-induced Cyclooxygenase-2 Expression in Macrophages^*

Sushil Kumar Pathak, Asima Bhattacharyya, Shresh Pathak, Chaitali Basak, Debabrata Mandal, Manikuntala Kundu, and Joyoti Basu

From the Department of Chemistry, Bose Institute, 93/1 Acharya Prafulla Chandra Road, Calcutta 700009, India

Understanding how pathogenic mycobacteria subvert the protective immune response is crucial to the development of strategies aimed at controlling mycobacterial infections. Prostaglandin E₂ exerts an immunosuppressive function in the context of mycobacterial infection. Because cyclooxygenase-2 (COX-2) is a rate-limiting enzyme in prostaglandin biosynthesis, there is a need to delineate the mechanisms through which pathogenic mycobacteria regulate COX-2 expression in macrophages. Our studies demonstrate that the NF-B and CRE elements of the COX-2 promoter are critical to Mycobacterium avium-induced COX-2 gene expression. M. avium-triggered signaling originates at the Toll-like receptor 2 (TLR2). Ras associates with TLR2 and activates the mitogen-activated protein kinase (MAPK) extracellular signal-regulated kinase (ERK), whereas tumor necrosis factor receptor-associated factor 6 (TRAF6)/transforming growth factor -activated kinase 1 (TAK1)-dependent signaling activates p38 MAPK. Both ERK and p38 MAPK activation converge to regulate the activation of mitogen- and stress-activated kinase 1 (MSK1). MSK1 mediates the phosphorylation of the transcription factor CREB accounting for its stimulatory effect on CRE-dependent gene expression. M. avium-triggered cytoplasmic NF-B activation following IB phosphorylation is necessary but not sufficient for COX-2 promoter-driven gene expression. MSK1 activation is also essential for M. avium-triggered NF-B-dependent gene expression, presumably mediating nucleosomal modifications. These studies demonstrate that the nuclear kinase MSK1 is necessary in regulating the pathogen-driven expression of a gene by controlling two transcription factors. The attenuation of MSK1 may therefore have potential benefit in restricting survival of pathogenic mycobacteria in macrophages.

Received for publication, August 27, 2004 , and in revised form, October 12, 2004.

^* This work was supported in part by grants from the National Bioscience Award for Career Development of the Department of Biotechnology, Government of India, the Department of Atomic Energy, Government of India, and the Department of Science and Technology, Government of India (to J. B.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Supported by a Junior Research Fellowship from the Council of Scientific and Industrial Research, Government of India.

To whom correspondence may be addressed. Tel.: 91-33-2350-6619; Fax: 91-33-2350-6790; E-mail: joyoti{at}vsnl.com (J. B.) or manikuntala{at}vsnl.net (M. K.).

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				D. Wang, M.-X. Guo, H.-M. Hu, Z.-Z. Zhao, H.-L. Qiu, H.-J. Shao, C.-G. Zhu, L. Xue, Y.-B. Shi, and W.-X. Li Human T-cell Leukemia Virus Type 1 Oncoprotein Tax Represses ZNF268 Expression through the cAMP-responsive Element-binding Protein/Activating Transcription Factor Pathway J. Biol. Chem., June 13, 2008; 283(24): 16299 - 16308. [Abstract] [Full Text] [PDF]

				M. Yamashita, T. Shinohara, S. Tsuji, Q. N. Myrvik, A. Nishiyama, R. A. Henriksen, and Y. Shibata Catalytically Inactive Cyclooxygenase 2 and Absence of Prostaglandin E2 Biosynthesis in Murine Peritoneal Macrophages following In Vivo Phagocytosis of Heat-Killed Mycobacterium bovis Bacillus Calmette-Guerin J. Immunol., November 15, 2007; 179(10): 7072 - 7078. [Abstract] [Full Text] [PDF]

				C.-H. Liu, F. S. Machado, R. Guo, K. E. Nichols, A. W. Burks, J. C. Aliberti, and X.-P. Zhong Diacylglycerol kinase {zeta} regulates microbial recognition and host resistance to Toxoplasma gondii J. Exp. Med., April 16, 2007; 204(4): 781 - 792. [Abstract] [Full Text] [PDF]

				S. Basu, S. K. Pathak, A. Banerjee, S. Pathak, A. Bhattacharyya, Z. Yang, S. Talarico, M. Kundu, and J. Basu Execution of Macrophage Apoptosis by PE_PGRS33 of Mycobacterium tuberculosis Is Mediated by Toll-like Receptor 2-dependent Release of Tumor Necrosis Factor-{alpha} J. Biol. Chem., January 12, 2007; 282(2): 1039 - 1050. [Abstract] [Full Text] [PDF]

				C. M. Olson, M. N. Hedrick, H. Izadi, T. C. Bates, E. R. Olivera, and J. Anguita p38 Mitogen-Activated Protein Kinase Controls NF-{kappa}B Transcriptional Activation and Tumor Necrosis Factor Alpha Production through RelA Phosphorylation Mediated by Mitogen- and Stress-Activated Protein Kinase 1 in Response to Borrelia burgdorferi Antigens Infect. Immun., January 1, 2007; 75(1): 270 - 277. [Abstract] [Full Text] [PDF]

				M. Yadav and J. S. Schorey The beta-glucan receptor dectin-1 functions together with TLR2 to mediate macrophage activation by mycobacteria Blood, November 1, 2006; 108(9): 3168 - 3175. [Abstract] [Full Text] [PDF]