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) All Versions of this Article: 292/6/L1385    most recent 00472.2006v1 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 ISI Web of Science 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 ISI Web of Science (3) Citing Articles via Google Scholar Google Scholar Articles by Tirumurugaan, K. G. Articles by Kannan, M. S. Search for Related Content PubMed PubMed Citation Articles by Tirumurugaan, K. G. Articles by Kannan, M. S.

TNF- induced CD38 expression in human airway smooth muscle cells: role of MAP kinases and transcription factors NF-B and AP-1

Departments of ¹Veterinary and Biomedical Sciences and ³Pharmacology, University of Minnesota, St. Paul, Minnesota; and ²Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania

Submitted 7 December 2006 ; accepted in final form 17 February 2007

In human airway smooth muscle (HASM) cells, the expression of CD38, which synthesizes the calcium-mobilizing molecule cyclic ADP-ribose, is augmented by TNF-, a cytokine implicated in asthma. We determined the role of mitogen-activated protein kinase (MAPK) in the activation of NF-B and AP-1 in the regulation of CD38 expression in HASM cells. In HASM cells exposed to TNF- (40 ng/ml), the inhibitors of extracellular signal-regulated kinase (ERK), p38, or c-Jun NH₂-terminal kinase (JNK) decreased CD38 expression and ADP-ribosyl cyclase activity. Transfection of HASM cells with a dominant negative MEK decreased while a wild-type ERK increased TNF--induced CD38 expression. Electrophoretic mobility shift assays (EMSAs) were performed using nuclear proteins and consensus sequences to detect the effect of the MAPKs on NF-B and AP-1 activation. EMSAs confirmed the role of p38 and JNK in mediating NF-B and AP-1 activation. Transfection of a dominant negative c-Jun decreased TNF--induced CD38 expression indicating involvement of AP-1. Stability of TNF--induced CD38 transcripts were determined in the presence of MAPK inhibitors after arresting the transcription with actinomycin D. Transcript stability decreased in the presence of ERK and p38 MAPK, but not the JNK, inhibitors. These results indicate that regulation of CD38 expression through p38 and JNK MAPKs involves NF-B and AP-1 activation, and ERK and p38 MAPKs also regulate expression posttranscriptionally through message stability.

extracellular signal-regulated kinase; p38; c-Jun NH₂-terminal kinase; electrophoretic mobility shift assays; ADP-ribosyl cyclase

This article has been cited by other articles:

				B. N. Kang, J. A. Jude, R. A. Panettieri Jr., T. F. Walseth, and M. S. Kannan Glucocorticoid regulation of CD38 expression in human airway smooth muscle cells: role of dual specificity phosphatase 1 Am J Physiol Lung Cell Mol Physiol, July 1, 2008; 295(1): L186 - L193. [Abstract] [Full Text] [PDF]

				B. Moynihan, B. Tolloczko, M.-C. Michoud, M. Tamaoka, P. Ferraro, and J. G. Martin MAP kinases mediate interleukin-13 effects on calcium signaling in human airway smooth muscle cells Am J Physiol Lung Cell Mol Physiol, July 1, 2008; 295(1): L171 - L177. [Abstract] [Full Text] [PDF]

				A. G. P. Guedes, J. A. Jude, J. Paulin, H. Kita, F. E. Lund, and M. S. Kannan Role of CD38 in TNF-{alpha}-induced airway hyperresponsiveness Am J Physiol Lung Cell Mol Physiol, February 1, 2008; 294(2): L290 - L299. [Abstract] [Full Text] [PDF]

				M. J. Sanderson, P. Delmotte, Y. Bai, and J. F. Perez-Zogbhi Regulation of Airway Smooth Muscle Cell Contractility by Ca2+ Signaling and Sensitivity Proceedings of the ATS, January 1, 2008; 5(1): 23 - 31. [Abstract] [Full Text] [PDF]