RT Journal Article
SR Electronic
T1 Selective Cyclooxygenase-2 Inhibition Does Not Alter Keratinocyte Wound Responses in the Mouse Epidermis after Abrasion
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 959
OP 967
DO 10.1124/jpet.102.044545
VO 304
IS 3
A1 Medora M. Hardy
A1 Eric A. G. Blomme
A1 Andrew Lisowski
A1 Kevin S. Chinn
A1 Amy Jones
A1 Janet M. Harmon
A1 Alan Opsahl
A1 Richard L. Ornberg
A1 Catherine S. Tripp
YR 2003
UL http://jpet.aspetjournals.org/content/304/3/959.abstract
AB The cyclooxygenase isoforms, COX-1 and COX-2, are the rate limiting enzymes in the biosynthesis of prostaglandin E2, a major prostaglandin involved in epidermal homeostasis and repair. Epidermal injury results in transient hyperplasia and induction of COX-2 expression. The role of COX-2 in this hyperplasia is unknown, however. In this study, we characterized the epidermal expression of COX isozymes following wounding by abrasion in SKH-1 mice using immunohistochemistry, in situ hybridization, and Western analysis. In addition, we evaluated pivotal keratinocyte functions necessary for the reparative hyperplasia, including proliferation by 5-bromo-2′deoxy-uridine labeling and differentiation by the expression of involucrin, keratin 1, and keratin 6. Although COX-1 expression in keratinocytes remained unchanged during wound healing, COX-2 expression was induced coincidentally with keratinocyte proliferation and keratin 6 expression, suggesting a role for COX-2 in epidermal repair. The role of COX-2 was also evaluated using the selective COX-2 inhibitor SC-791 and the traditional COX inhibitors indomethacin and diclofenac. Neither inhibitor altered keratinocyte proliferation or differentiation following abrasion, in contrast to dexamethasone, which delayed these responses. Our results indicated that, although COX-2 expression was coincident with transient epidermal hyperplasia and keratinocyte proliferation/differentiation during the healing of epidermal injury, it does not play a pivotal role in this repair process. The American Society for Pharmacology and Experimental Therapeutics