Polyamine-mediated reduction in human airway epithelial migration in response to wounding is PGE2 dependent through decreases in COX-2 and cPLA2 protein levels.
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 approximately 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.
Cowan
Mark J
MJ
Department of Medicine, Division of Pulmonary and Critical Care Medicine, The University of Maryland, 10 North Greene St., Rm. 3D122, Baltimore, 21201, USA. mcowan@medicine.umaryland.edu
Coll
Timothy
T
Shelhamer
James H
JH
D015317:Biogenic Polyamines / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects* / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D015232:Dinoprostone / Q000378:metabolism*; D004336:Drug Antagonism; D004338:Drug Combinations; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D007052:Ibuprofen / Q000494:pharmacology; D009955:Ornithine Decarboxylase / Q000235:genetics; D065108:Ornithine Decarboxylase Inhibitors; D010741:Phospholipases A / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000494:pharmacology; D020545:Respiratory Mucosa / Q000187:drug effects* / Q000378:metabolism; D014945:Wound Healing / Q000187:drug effects / Q000502:physiology
D015317:Biogenic Polyamines; D004338:Drug Combinations; D004791:Enzyme Inhibitors; D065108:Ornithine Decarboxylase Inhibitors; D034741:RNA, Small Interfering; D051546:Cyclooxygenase 2; D010741:Phospholipases A; D009955:Ornithine Decarboxylase; D015232:Dinoprostone; D007052:Ibuprofen