help button home button
AJRCMB
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS

Published ahead of print on January 31, 2003, doi:10.1165/rcmb.2002-0254OC
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
2002-0254OCv1
29/1/19    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 Google Scholar
Google Scholar
Right arrow Articles by Goncharova, E. A.
Right arrow Articles by Panettieri, R. A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Goncharova, E. A.
Right arrow Articles by Panettieri, R. A., Jr.
American Journal of Respiratory Cell and Molecular Biology. Vol. 29, pp. 19-27, 2003
© 2003 American Thoracic Society
DOI: 10.1165/rcmb.2002-0254OC

Cyclic AMP-Mobilizing Agents and Glucocorticoids Modulate Human Smooth Muscle Cell Migration

Elena A. Goncharova, Charlotte K. Billington, Carla Irani, Alexander V. Vorotnikov, Vsevolod A. Tkachuk, Raymond B. Penn, Vera P. Krymskaya and Reynold A. Panettieri, Jr.

Pulmonary, Allergy, and Critical Care Division, Department of Medicine, University of Pennsylvania; Division of Critical Care, Pulmonary, Allergic & Immunologic Diseases, Jefferson Medical College, and Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania; and Laboratory of Cell Motility, Laboratory of Molecular Endocrinology, Institute of Experimental Cardiology, Russian Cardiology Research Center, Moscow, Russia

Address correspondence to: Reynold A. Panettieri, Jr., M.D., Pulmonary, Allergy and Critical Care Division, University of Pennsylvania, 421 Curie Boulevard, Room 805 BRB II/III, Philadelphia, PA 19104-6160. E-mail: rap{at}mail.med.upenn.edu

Hyperplasia and cell migration of smooth muscle are features of both airway and pulmonary vascular diseases. The precise cellular and molecular mechanisms that regulate smooth muscle migration in the lungs remain unknown. In this study, we examined the effect of cAMP-mobilizing agents and steroids on smooth muscle cell migration. Platelet-derived growth factor (PDGF), transforming growth factor-{alpha}, vascular endothelial growth factor, and basic fibroblast growth factor significantly stimulated cell migration in pulmonary vascular smooth muscle (PVSM) cells. Airway smooth muscle (ASM) migration was also stimulated by PDGF, transforming growth factor-{alpha}, and basic fibroblast growth factor, but vascular endothelial growth factor was without effect. Interestingly, the smooth muscle mitogen thrombin did not stimulate migration of either cell type. Agents capable of elevating intracellular cAMP inhibited basal (unstimulated) cell migration in both cell types, whereas their effects on PDGF-stimulated migration were more variable. Prostaglandin E2, salmeterol, and the phosphodiesterase type 4 inhibitor cilomolast inhibited basal ASM and PVSM migration by 30–60%. Prostaglandin E2 and cilomolast also inhibited PDGF-stimulated migration of ASM and PVSM cells, but salmeterol was without effect. Preincubation of ASM cells with dexamethasone or fluticasone inhibited basal and PDGF-stimulated migration, and enabled an inhibitory effect of salmeterol on PDGF-induced cell migration. Steroids alone did not stimulate cAMP production or cAMP/PKA-dependent gene transcription (CRE-Luc activity), but slightly augmented salmeterol-stimulated CRE-Luc activity. Collectively, these findings demonstrate that cAMP-mobilizing agents and steroids modulate human smooth muscle cell migration, likely by distinct mechanisms.

Abbreviations: airway smooth muscle, ASM • basic fibroblast growth factor, bFGF • cAMP/PKA-dependent gene transcription, CRE-Luc activity • fetal bovine serum, FBS • phosphodiesterase type 4, PDE4 • platelet-derived growth factor, PDGF • prostaglandin E2, PGE2 • pulmonary vascular smooth muscle, PVSM • transforming growth factor-{alpha}, TGF-{alpha} • vascular endothelial growth factor, VEGF







HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Proc. Am. Thorac. Soc. Am. J. Respir. Crit. Care Med.
Copyright © 2003 American Thoracic Society.
  ATS Best of the Web