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

This Article Full Text Free Full Text (PDF) Free All Versions of this Article: 97/6/2154    most recent 00752.2003v1 Submit a response Alert me when this article is cited Alert me when eLetters are posted 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 (11) Citing Articles via Google Scholar Google Scholar Articles by Sakai, H. Articles by Misawa, M. Search for Related Content PubMed PubMed Citation Articles by Sakai, H. Articles by Misawa, M.

Involvement of p42/44 MAPK and RhoA protein in augmentation of ACh-induced bronchial smooth muscle contraction by TNF- in rats

Department of Pharmacology, School of Pharmacy, Hoshi University, Tokyo 142-8501, Japan

Submitted 22 July 2003 ; accepted in final form 23 June 2004

Bronchial asthma is characterized by chronic inflammation of airway tissues and nonspecific airway hyperresponsiveness (AHR), but the underlying mechanisms of AHR have yet to be elucidated. Recently, tumor necrosis factor- (TNF-) has been identified as a proinflammatory cytokine that might be important in the hyperresponsiveness of airway tissue. We have investigated the effects of SB-203580 (a p38 MAPK inhibitor), U-0126 (an inhibitor of p42/44 MAPK activation), and cycloheximide (an inhibitor of protein synthesis) on TNF--augmented ACh-induced bronchial smooth muscle contraction. We have also investigated the phosphorylation of p42/44 MAPK and upregulation of RhoA protein by TNF-. Treatment of rat bronchial smooth muscles with TNF- (300 and 1,000 ng/ml for 24 h) resulted in a significant upward shift in the concentration-response curve to ACh, but not to high K⁺, compared with control tissues. The effect of TNF- was completely blocked by pretreatment with U-0126 or cycloheximide, but not with SB-203580. Immunoblotting demonstrated that p42/44 MAPK was phosphorylated and RhoA protein was increased in bronchial tissue by TNF-. Furthermore, the TNF--induced upregulation of RhoA protein was abolished by U-0126 pretreatment. In conclusion, we suggest that TNF- might be one of the important mediators involved in the pathogenesis of augmented bronchial smooth muscle contractility in AHR. For the first time, we have demonstrated that augmentation of ACh-induced contractile response evoked by TNF- was mediated by synthesis of protein, such as RhoA, through activation of p42/44, but not p38 MAPK, in rat bronchial smooth muscle.

acetylcholine asthma

This article has been cited by other articles:

				C. Morin, M. Sirois, V. Echave, M. M. Gomes, and E. Rousseau EET Displays Anti-Inflammatory Effects in TNF-{alpha} Stimulated Human Bronchi: Putative Role of CPI-17 Am. J. Respir. Cell Mol. Biol., February 1, 2008; 38(2): 192 - 201. [Abstract] [Full Text] [PDF]

				C. Liu, T. Tazzeo, and L. J. Janssen Isoprostane-induced airway hyperresponsiveness is dependent on internal Ca2+ handling and Rho/ROCK signaling Am J Physiol Lung Cell Mol Physiol, December 1, 2006; 291(6): L1177 - L1184. [Abstract] [Full Text] [PDF]

				M. Fayon, M. Rebola, P. Berger, S. Daburon, O. Ousova, F. Lavrand, B. Moukaila, W. Pujol, J. L. Taupin, A. Labbe, et al. Increased secretion of leukemia inhibitory factor by immature airway smooth muscle cells enhances intracellular signaling and airway contractility Am J Physiol Lung Cell Mol Physiol, August 1, 2006; 291(2): L244 - L251. [Abstract] [Full Text] [PDF]