Celecoxib inhibits early cutaneous wound healing

J Surg Res. 2015 Apr;194(2):717-724. doi: 10.1016/j.jss.2014.12.026. Epub 2014 Dec 18.

Abstract

Background: Cyclooxygenase-2 (COX-2) is an inducible enzyme that is rapidly upregulated in response to injury, resulting in the production of prostaglandin E2 (PGE2), a primary mediator of inflammation and wound healing. The selective COX-2 inhibitor, celecoxib, is was used to treat pain and inflammation. When used to treat injuries, we postulated that loss of PGE2 activity by COX-2 inhibition would have detrimental effects on wound healing. Our objective was to study the effect of selective COX-2 inhibition with celecoxib on cutaneous wound healing.

Materials and methods: C57BL/6J mice with uniform full-thickness wounds (1 cm(2)) to their dorsum were fed diet with or without celecoxib (1500 ppm). Wound closure analysis measured wound contraction, reepithelialization, and open wound as a percentage of the initial wound area, and was quantified by planimetry. Wounds were excised en bloc at day 7 to examine cellular proliferation, angiogenesis, cytokine production, and extracellular matrix (ECM) formation.

Results: Celecoxib-induced reduction in wound PGE2 levels was documented by enzyme-linked immunosorbent assay on day 7 after wounding. Wound contraction and reepithelialization were significantly reduced by celecoxib treatment, resulting in a 20% greater open wound area at day 7 (P < 0.05). In response to celecoxib treatment, immunohistochemistry analysis showed epithelial cell proliferation, angiogenesis, and ECM components including collagen and myofibroblasts were significantly decreased.

Conclusions: Wound healing is significantly delayed by celecoxib treatment. These data indicate that COX-2 and its downstream product PGE2 modulate the activity of multiple essential functions of the inflammatory stroma, including epithelial proliferation, angiogenesis, and ECM production. As a result, reepithelialization and wound closure are delayed by celecoxib treatment. These findings have potential clinical implications in postoperative wound management.

Keywords: Angiogenesis; COX-2; Celecoxib; Myofibroblasts; NSAIDs; PGE(2); Reepithelialization; Wound healing.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Celecoxib
  • Cell Proliferation / drug effects
  • Cyclooxygenase 2 Inhibitors / adverse effects*
  • Extracellular Matrix / drug effects
  • Extracellular Matrix / metabolism
  • Female
  • Mice, Inbred C57BL
  • Neovascularization, Physiologic / drug effects
  • Pyrazoles / adverse effects*
  • Sulfonamides / adverse effects*
  • Wound Healing / drug effects*

Substances

  • Cyclooxygenase 2 Inhibitors
  • Pyrazoles
  • Sulfonamides
  • Celecoxib