Submitted on October 6, 2005
Accepted on May 29, 2006
Polyamine-mediated reduction in human airway epithelial migration in response to wounding is PGE2-dependent through decreases in COX-2 and cPLA2 protein levels
Mark J. Cowan1*, Timothy Coll2, and James H. Shelhamer3
1 Department of Medicine, Division of Pulmonary and Critical Care Medicine, The University of Maryland School of Medicine, Baltimore, Maryland, United States
2 Medicine, The University of Maryland School of Medicine, Baltimore, Maryland, United States
3 CC, CCMD, The National Institutes of Health, Bethesda, Maryland, United States
* To whom correspondence should be addressed. E-mail: mcowan{at}medicine.umaryland.edu.
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 about 75%. Restoration of normal migration responses is achieved in the polyamine depleted system either by exogenous reconstitution of polyamines or the addition of prostaglandin E2 (PGE2). However, only PGE2 was able to restore migration in the cyclooxygenase inhibited systems. Western blot for COX-2 and cytosolic phospholipase A2 protein levels, and ELISA's for PGE2 secretion demonstrate dramatic increases over 24-48 hours 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 PGE2 production in response to injury. This may be brought about by decreases in cPLA2 and COX-2 protein levels.
