title: Selective cyclooxygenase-2 inhibition does not affect the healing of cutaneous full-thickness incisional wounds in SKH-1 mice.
abstract: BACKGROUND
  The inducible cyclooxygenase-2 (COX-2) enzyme is upregulated in inflammatory diseases, as well as in epithelial cancers, and has an established role in angiogenesis and tissue repair.
  
  
  OBJECTIVE
  Because of these physiological effects and the widespread use of the selective COX-2 inhibitor, celecoxib, we wanted to determine if inhibition of COX-2 would affect incisional skin wound healing.
  
  
  METHODS
  Using a cutaneous full-thickness, sutured, incisional wound model in hairless SKH-1 mice, we evaluated the role of COX-2 in the wound healing process by comparing the effects of a nonselective COX inhibitor, diclofenac, with a selective COX-2 inhibitor, SC-791. Healing was monitored for up to 28 days postincision histologically and for recovery of wound strength.
  
  
  RESULTS
  COX-2 expression was observed over the first week of healing, peaking at day 3 and was not affected by treatment with the selective COX-2 or nonselective COX inhibitors. Infiltrating macrophages, as well as keratinocytes and dermal fibroblasts at the wound site, expressed COX-2. Neither selective COX-2, nor nonselective COX inhibition had a significant effect on the macroscopic or microscopic morphology of the wounds, whereas dexamethasone treatment resulted in epidermal and granulation tissue atrophy. In addition, neither selective COX-2, nor nonselective COX inhibition altered keratinocyte proliferation and differentiation, dermal angiogenesis or the recovery of wound tensile strength, whereas dexamethasone reduced the tensile strength of the wounds by 30-38% throughout the healing period.
  
  
  CONCLUSIONS
  These data indicate that selective COX-2 inhibition does not affect the healing of surgical skin wounds.
authors.affiliation: Department of Global Toxicology, Pharmacia Corporation, 4901 Searle Parkway, Skokie, IL 60077, USA. eric.blomme@pharmacia.com
authors.forename: E A G
authors.initials: EA
authors.lastname: Blomme
authors.forename: K S
authors.initials: KS
authors.lastname: Chinn
authors.forename: M M
authors.initials: MM
authors.lastname: Hardy
authors.forename: J J
authors.initials: JJ
authors.lastname: Casler
authors.forename: S H
authors.initials: SH
authors.lastname: Kim
authors.forename: A C
authors.initials: AC
authors.lastname: Opsahl
authors.forename: W A
authors.initials: WA
authors.lastname: Hall
authors.forename: D
authors.initials: D
authors.lastname: Trajkovic
authors.forename: K N
authors.initials: KN
authors.lastname: Khan
authors.forename: C S
authors.initials: CS
authors.lastname: Tripp
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D015153:Blotting, Western; D002455:Cell Division; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000378:metabolism*; D003907:Dexamethasone / Q000494:pharmacology; D005260:Female; D017403:In Situ Hybridization / Q000379:methods; D007527:Isoenzymes / Q000378:metabolism*; D015603:Keratinocytes / Q000502:physiology; D051379:Mice; D008815:Mice, Inbred Strains; D008819:Mice, Nude; D011233:Precipitin Tests; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D012867:Skin / Q000187:drug effects / Q000201:enzymology / Q000293:injuries*; D014945:Wound Healing / Q000187:drug effects / Q000502:physiology*
chemical_list: D000893:Anti-Inflammatory Agents; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D003907:Dexamethasone; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases