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

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map 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 Lim, W. Articles by Kumar, A. Search for Related Content PubMed PubMed Citation Articles by Lim, W. Articles by Kumar, A.

Regulation of B7.1 Costimulatory Molecule Is Mediated by the IFN Regulatory Factor-7 through the Activation of JNK in Lipopolysaccharide-Stimulated Human Monocytic Cells¹

Wilfred Lim, Katrina Gee, Sasmita Mishra and Ashok Kumar^2,*,,

^* Departments of Pathology and Laboratory Medicine and Department of Biochemistry, Microbiology, and Immunology, University of Ottawa, and Division of Virology and Molecular Immunology, Research Institute, Children’s Hospital of Eastern Ontario, Ottawa, Canada

The engagement of CD28 or CTLA-4 with B7.1 provides the essential second costimulatory signal that regulates the development of immune responses, including T cell activation, differentiation, and induction of peripheral tolerance. The signaling molecules and the transcription factors involved in B7.1 regulation are poorly understood. In this study we investigated the role of MAPKs in the regulation of LPS-induced B7.1 expression in human monocytes and the promonocytic THP-1 cells. Our results show that LPS-induced B7.1 expression in monocytic cells did not involve the activation of either p38 or ERKs. Using the JNK-specific inhibitor SP600125, small interfering RNAs specific for JNK1 and JNK2, and agents such as dexamethasone that inhibit JNK activation, we determined that LPS-induced B7.1 expression was regulated by JNK MAPK in both monocytes and THP-1 cells. In addition, we identified a distinct B7.1-responsive element corresponding to the IFN regulatory factor-7 (IRF-7) binding site in the B7.1 promoter responsible for the regulation of LPS-induced B7.1 transcription. Furthermore, SP600125 and dexamethasone inhibited LPS-induced IRF-7 activity. Taken together, these results suggest that LPS-induced B7.1 transcription in human monocytic cells may be regulated by JNK-mediated activation of the IRF-7 transcription factor.

This article has been cited by other articles:

				W. Ma, S. Mishra, K. Gee, J. P. Mishra, D. Nandan, N. E. Reiner, J. B. Angel, and A. Kumar Cyclosporin A and FK506 Inhibit IL-12p40 Production through the Calmodulin/Calmodulin-dependent Protein Kinase-activated Phosphoinositide 3-Kinase in Lipopolysaccharide-stimulated Human Monocytic Cells J. Biol. Chem., May 4, 2007; 282(18): 13351 - 13362. [Abstract] [Full Text] [PDF]

				S. Mishra, J. P. Mishra, and A. Kumar Activation of JNK-dependent Pathway Is Required for HIV Viral Protein R-induced Apoptosis in Human Monocytic Cells: INVOLVEMENT OF ANTIAPOPTOTIC BCL2 AND c-IAP1 GENES J. Biol. Chem., February 16, 2007; 282(7): 4288 - 4300. [Abstract] [Full Text] [PDF]

				J. M. Gee, A. Kalil, C. Shea, and K. J. Becker Lymphocytes: Potential Mediators of Postischemic Injury and Neuroprotection Stroke, February 1, 2007; 38(2): 783 - 788. [Abstract] [Full Text] [PDF]