help button home button
AJRCMB
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Published ahead of print on August 7, 2008, doi:10.1165/rcmb.2008-0162OC
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
2008-0162OCv1
40/2/159    most recent
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 arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Chiba, Y.
Right arrow Articles by Misawa, M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Chiba, Y.
Right arrow Articles by Misawa, M.
American Journal of Respiratory Cell and Molecular Biology. Vol. 40, pp. 159-167, 2009
© 2009 American Thoracic Society
DOI: 10.1165/rcmb.2008-0162OC

Interleukin-13 Augments Bronchial Smooth Muscle Contractility with an Up-Regulation of RhoA Protein

Yoshihiko Chiba1, Shuji Nakazawa1, Michiko Todoroki1, Koji Shinozaki1, Hiroyasu Sakai1 and Miwa Misawa1

1 Department of Pharmacology, School of Pharmacy, Hoshi University, Tokyo, Japan

Correspondence and requests for reprints should be addressed to Yoshihiko Chiba, Ph.D., Department of Pharmacology, School of Pharmacy, Hoshi University, 2-4-41 Ebara, Shinagawa-ku, Tokyo 142-8501, Japan. E-mail: chiba{at}hoshi.ac.jp

Interleukin-13 (IL-13) is one of the central mediators for development of airway hyperresponsiveness in asthma. However, its effect on bronchial smooth muscle (BSM) is not well known. Recent studies revealed an involvement of RhoA/Rho-kinase in BSM contraction, and this pathway has now been proposed as a new target for asthma therapy. To elucidate the role of IL-13 on the induction of BSM hyperresponsiveness, effects of IL-13 on contractility and RhoA expression in BSMs were investigated. Male BALB/c mice were sensitized and repeatedly challenged with ovalbumin antigen. In the repeatedly antigen-challenged mice, marked airway inflammation and BSM hyperresponsiveness with an up-regulation of IL-13 in bronchoalveolar lavage fluids were observed. In cultured human BSM cells, IL-13 caused an up-regulation of RhoA. The IL-13–induced up-regulation of RhoA was inhibited by leflunomide, an inhibitor of signal transducer and activator of transcription 6 (STAT6). In isolated BSM tissues of naive mice, the contractility was significantly enhanced by organ culture in the presence of IL-13. Moreover, in vivo treatment of airways with IL-13 by intranasal instillation caused a BSM hyperresponsiveness with an up-regulation of RhoA in naive mice. These findings suggest that IL-13/STAT6 signaling is critical for development of antigen-induced BSM hyperresponsiveness and that agents that specifically inhibit this pathway in BSM may provide a novel strategy for the treatment of asthma.

Key Words: asthma • airway hyperresponsiveness • bronchial smooth muscle • interleukin-13 • RhoA


CLINICAL RELEVANCE

Our results suggest that IL-13/STAT6 signaling is critical in development of antigen-induced bronchial smooth muscle hyperresponsiveness, and that agents which specifically inhibit this pathway may provide a novel strategy for the treatment of allergic bronchial asthma.

 



This article has been cited by other articles:


Home page
 PhysiologyHome page
S. Puetz, L. T. Lubomirov, and G. Pfitzer
Regulation of Smooth Muscle Contraction by Small GTPases
Physiology, December 1, 2009; 24(6): 342 - 356.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Cell Mol. Bio.Home page
Y. Chiba, M. Todoroki, Y. Nishida, M. Tanabe, and M. Misawa
A Novel STAT6 Inhibitor AS1517499 Ameliorates Antigen-Induced Bronchial Hypercontractility in Mice
Am. J. Respir. Cell Mol. Biol., November 1, 2009; 41(5): 516 - 524.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
Y. Chiba, S. Sato, M. Hanazaki, H. Sakai, and M. Misawa
Inhibition of geranylgeranyltransferase inhibits bronchial smooth muscle hyperresponsiveness in mice
Am J Physiol Lung Cell Mol Physiol, November 1, 2009; 297(5): L984 - L991.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Crit. Care Med.Home page
Y. Chiba, M. Tanabe, K. Goto, H. Sakai, and M. Misawa
Down-Regulation of miR-133a Contributes to Up-Regulation of RhoA in Bronchial Smooth Muscle Cells
Am. J. Respir. Crit. Care Med., October 15, 2009; 180(8): 713 - 719.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
A. Margulis, K. H. Nocka, A. M. Brennan, B. Deng, M. Fleming, S. J. Goldman, and M. T. Kasaian
Mast Cell-Dependent Contraction of Human Airway Smooth Muscle Cell-Containing Collagen Gels: Influence of Cytokines, Matrix Metalloproteases, and Serine Proteases
J. Immunol., August 1, 2009; 183(3): 1739 - 1750.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Proc. Am. Thorac. Soc. Am. J. Respir. Crit. Care Med.
Copyright © 2009 American Thoracic Society. 		  Membership Renewal