Celecoxib inhibits early cutaneous wound healing.

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.

• Authors: Mark Fairweather, Yvonne I Heit, Justin Buie, Laura M Rosenberg, Alexandra Briggs, Dennis P Orgill, Monica M Bertagnolli
• Journal: The Journal of surgical research (J Surg Res) Vol. 194 Issue 2 Pg. 717-724 (Apr 2015) ISSN: 1095-8673 [Electronic] United States
• PMID: 25588948 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: Copyright © 2015 Elsevier Inc. All rights reserved.

Chemical References

• Cyclooxygenase 2 Inhibitors
• Pyrazoles
• Sulfonamides
• Celecoxib

Topics

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