Prostaglandin E-2 regulates wound closure in airway epithelium

Repair of the airway epithelium after injury is critical for the maintenanc e 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 st imulating or inhibiting COX metabolites would affect wound closure in monol ayers of cultured AECs. Inhibiting COX with indomethacin resulted in a dose -dependent inhibition of wound closure in human and feline AECs. Specific i nhibitors for both COX-1 and COX-2 isoforms impaired wound healing. Inhibit ors of 5-lipoxygenase did not affect wound closure in these cells. The addi tion of prostaglandin E-2 (PGE(2)) eliminated the inhibition due to indomet hacin treatment, and the exogenous application of PGE(2) stimulated wound c losure 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.