help button home button
AJRCMB
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Published ahead of print on February 22, 2007, doi:10.1165/rcmb.2006-0383OC
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Online Supplement
Right arrow All Versions of this Article:
2006-0383OCv1
36/6/757    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 Roviezzo, F.
Right arrow Articles by Cirino, G.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Roviezzo, F.
Right arrow Articles by Cirino, G.
American Journal of Respiratory Cell and Molecular Biology. Vol. 36, pp. 757-762, 2007
© 2007 American Thoracic Society
DOI: 10.1165/rcmb.2006-0383OC

Sphingosine-1-Phosphate/Sphingosine Kinase Pathway Is Involved in Mouse Airway Hyperresponsiveness

Fiorentina Roviezzo*, Annarita Di Lorenzo*, Mariarosaria Bucci, Vincenzo Brancaleone, Valentina Vellecco, Marilisa De Nardo, Donatella Orlotti, Raffaele De Palma, Francesco Rossi, Bruno D'Agostino and Giuseppe Cirino

Dipartimento di Farmacologia Sperimentale, Università di Napoli Federico II; Dipartimento di Medicina Sperimentale, Sezione di Farmacologia L. Donatelli, Seconda Università degli Studi di Napoli; and Dipartimento di Internistica Clinica e Sperimentale, Seconda Università di Napoli, Napoli, Italy

Correspondence and requests for reprints should be addressed to Giuseppe Cirino, Ph.D., Dipartimento di Farmacologia Sperimentale, via Domenico Montesano 49, 80131 Napoli, Italy. E-mail: cirino{at}unina.it

Sphingosine-1-phosphate (S1P) has been shown to regulate numerous and diverse cell functions, including smooth muscle contraction. Here we assessed the role of S1P/Sphingosine kinase (SPK) pathway in the regulation of bronchial tone. Our objective was to determine, using an integrated pharmacologic and molecular approach, (1) the role of S1P as endogenous modulator of the bronchial tone, and (2) the linkage between S1P pathway and bronchial hyperresponsiveness. We evaluated S1P effects on isolated bronchi and whole lungs, harvested from Balb/c mice sensitized to ovalbumin (OVA) versus vehicle-treated mice, by measuring bronchial reactivity and lung resistance. We found that S1P administration on nonsensitized mouse bronchi does not cause any direct effect on bronchial tone, while a significant increase in Ach-induced contraction occurs after S1P challenge. Conversely, in OVA-sensitized mice S1P/SPK pathway triggers airway hyperesponsiveness. Indeed, S1P causes a dose-dependent contraction of isolated bronchi. Similarly, in the whole lung system S1P increased airway resistance only in OVA-sensitized mice. The action on bronchi of S1P is coupled to an enhanced expression of SPK1 and SPK2 as well as of S1P2 and S1P3 receptors. In these experiments the key role for S1P/SPK in hyperreactivity has been confirmed by pharmacologic modulation of SPKs. S1P/SPK pathway does not seem to play a major role in physiologic conditions, while it may become critical in pathologic conditions. These results open new windows for therapeutic strategies in diseases like asthma.

Key Words: S1P • sphingosine kinase • bronchus • hyperresponsiveness


CLINICAL RELEVANCE

Sphingosine-1-phosphate (S1P) is present in bronchoalveolar lavage of patients with asthma. Here we have demonstrated that S1P/sphongosine kinase (SPK) pathway is involved in airway hyperresponsiveness. Our data indicate that S1P/SPK pathway can represent a target in designing new therapies.

 



This article has been cited by other articles:


Home page
 J. Pharmacol. Exp. Ther.Home page
S. M. Camp, R. Bittman, E. T. Chiang, L. Moreno-Vinasco, T. Mirzapoiazova, S. Sammani, X. Lu, C. Sun, M. Harbeck, M. Roe, et al.
Synthetic Analogs of FTY720 [2-Amino-2-(2-[4-octylphenyl]ethyl)-1,3-propanediol] Differentially Regulate Pulmonary Vascular Permeability in Vivo and in Vitro
J. Pharmacol. Exp. Ther., October 1, 2009; 331(1): 54 - 64.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Crit. Care Med.Home page
S. Uhlig and E. Gulbins
Sphingolipids in the Lungs
Am. J. Respir. Crit. Care Med., December 1, 2008; 178(11): 1100 - 1114.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
T. Nishiuma, Y. Nishimura, T. Okada, E. Kuramoto, Y. Kotani, S. Jahangeer, and S.-i. Nakamura
Inhalation of sphingosine kinase inhibitor attenuates airway inflammation in asthmatic mouse model
Am J Physiol Lung Cell Mol Physiol, June 1, 2008; 294(6): L1085 - L1093.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
W.-Q. Lai, H. H. Goh, Z. Bao, W. S. F. Wong, A. J. Melendez, and B. P. Leung
The Role of Sphingosine Kinase in a Murine Model of Allergic Asthma
J. Immunol., March 15, 2008; 180(6): 4323 - 4329.
[Abstract] [Full Text] [PDF]

Home page
 J. Pharmacol. Exp. Ther.Home page
E. Masini, L. Giannini, S. Nistri, L. Cinci, R. Mastroianni, W. Xu, S. A. A. Comhair, D. Li, S. Cuzzocrea, G. M. Matuschak, et al.
Ceramide: a Key Signaling Molecule in a Guinea Pig Model of Allergic Asthmatic Response and Airway Inflammation
J. Pharmacol. Exp. Ther., February 1, 2008; 324(2): 548 - 557.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Proc. Am. Thorac. Soc. Am. J. Respir. Crit. Care Med.
Copyright © 2007 American Thoracic Society. 		  SOTA, FL