Polyamine-mediated reduction in human airway epithelial migration in response to wounding is PGE2 dependent through decreases in COX-2 and cPLA2 protein levels

• Published in: Journal of applied physiology (1985) 2006-10, Vol.101 (4), p.1127-1135
• Main Authors: Cowan, Mark J, Coll, Timothy, Shelhamer, James H
• Format: Article
• Language: English
• Subjects: Biogenic Polyamines - antagonists & inhibitors; Biogenic Polyamines - pharmacology; Biological and medical sciences; Cell Line; Cell Movement - drug effects; Cell Movement - physiology; Cell Survival - drug effects; Cyclooxygenase 2 - metabolism; Dinoprostone - metabolism; Drug Antagonism; Drug Combinations; Enzyme Inhibitors - pharmacology; Fundamental and applied biological sciences. Psychology; Humans; Ibuprofen - pharmacology; Ornithine Decarboxylase - genetics; Ornithine Decarboxylase Inhibitors; Phospholipases A - genetics; Phospholipases A - metabolism; Respiratory Mucosa - drug effects; Respiratory Mucosa - metabolism; RNA, Small Interfering - pharmacology; Wound Healing - drug effects; Wound Healing - physiology
• ISSN: 8750-7587; 1522-1601
• DOI: 10.1152/japplphysiol.01287.2005

1 Department of Medicine, Division of Pulmonary and Critical Care Medicine, The University of Maryland School of Medicine, Baltimore, and 2 Critical Care Medicine Department, The National Institutes of Health, Bethesda, Maryland Submitted 6 October 2005 ; accepted in final form 29 May 2006 Both ornithine decarboxylase inhibition to deplete polyamines and cyclooxygenase inhibition diminish the migration response to injury of human airway epithelial cells in tissue culture monolayers by 75%. Restoration of normal migration responses is achieved in the polyamine depleted system either by exogenous reconstitution of polyamines or the addition of prostaglandin E 2 (PGE 2 ). However, only PGE 2 was able to restore migration in the cyclooxygenase-inhibited systems. Western blot for cyclooxygenase-2 and cytosolic phospholipase A 2 protein levels and ELISAs for PGE 2 secretion demonstrate dramatic increases over 24–48 h after monolayer wounding. These increases are completely abolished by polyamine depletion or cyclooxygenase inhibition. We conclude that polyamine inhibition decreases cellular migration in response to injury in airway epithelial cells at least in part through inhibiting normal PGE 2 production in response to injury. This may be brought about by decreases in cytosolic phospholipase A 2 and cyclooxygenase-2 protein levels. ornithine decarboxylase; putrescine, spermidine; spermine; restitution; airway epithelial cell; prostaglandin E 2 ; cytosolic phospholipase A 2 ; cyclooxygenase; asthma; chronic obstructive pulmonary disease Address for reprint requests and other correspondence: M. J. Cowan, Dept. of Medicine, The Univ. of Maryland, 10 North Greene St., Rm. 3D122, Baltimore, MD 21201 (e-mail: mcowan{at}medicine.umaryland.edu )