Prostaglandin E(2) regulates wound closure in airway epithelium.
Repair of the airway epithelium after injury is critical for the maintenance of barrier function and the limitation of airway hyperreactivity. Airway epithelial cells (AECs) metabolize arachidonic acid to biologically active eicosanoids via the enzyme cyclooxygenase (COX). We investigated whether stimulating or inhibiting COX metabolites would affect wound closure in monolayers of cultured AECs. Inhibiting COX with indomethacin resulted in a dose-dependent inhibition of wound closure in human and feline AECs. Specific inhibitors for both COX-1 and COX-2 isoforms impaired wound healing. Inhibitors of 5-lipoxygenase did not affect wound closure in these cells. The addition of prostaglandin E(2) (PGE(2)) eliminated the inhibition due to indomethacin treatment, and the exogenous application of PGE(2) stimulated wound closure in a dose-dependent manner. Inhibition of COX with indomethacin only at initial time points resulted in a sustained inhibition of wound closure, indicating that prostanoids are involved in early wound repair processes such as spreading and migration. These differences in wound closure may be important if arachidonic acid metabolism and eicosanoid concentrations are altered in disease states such as asthma.
Savla
U
U
Department of Biomedical Engineering, Illinois 60611, USA.
Appel
H J
HJ
Sporn
P H
PH
Waters
C M
CM
D000818:Animals; D002415:Cats; D002478:Cells, Cultured; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D015232:Dinoprostone / Q000494:pharmacology / Q000502:physiology*; D004848:Epithelium / Q000503:physiopathology; D007213:Indomethacin / Q000494:pharmacology; D018078:Receptors, Prostaglandin E / Q000502:physiology; D058306:Receptors, Prostaglandin E, EP1 Subtype; D058309:Receptors, Prostaglandin E, EP4 Subtype; D013997:Time Factors; D014132:Trachea / Q000503:physiopathology*; D014945:Wound Healing / Q000187:drug effects / Q000502:physiology*
D016861:Cyclooxygenase Inhibitors; C545635:PTGER1 protein, human; C545650:PTGER4 protein, human; D018078:Receptors, Prostaglandin E; D058306:Receptors, Prostaglandin E, EP1 Subtype; D058309:Receptors, Prostaglandin E, EP4 Subtype; D015232:Dinoprostone; D007213:Indomethacin