title: 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.
  
  
  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.affiliation: Division of Surgical Oncology, Department of Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
authors.forename: Mark
authors.initials: M
authors.lastname: Fairweather
authors.affiliation: Department of Plastic, Aesthetic and Hand Surgery, University of Magdeburg, Germany.
authors.forename: Yvonne I
authors.initials: YI
authors.lastname: Heit
authors.affiliation: Division of Surgical Oncology, Department of Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
authors.forename: Justin
authors.initials: J
authors.lastname: Buie
authors.affiliation: Division of Surgical Oncology, Department of Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
authors.forename: Laura M
authors.initials: LM
authors.lastname: Rosenberg
authors.affiliation: Division of Surgical Oncology, Department of Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Briggs
authors.affiliation: Division of Plastic Surgery, Department of Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
authors.forename: Dennis P
authors.initials: DP
authors.lastname: Orgill
authors.affiliation: Division of Surgical Oncology, Department of Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts. Electronic address: mbertagnolli@partners.org.
authors.forename: Monica M
authors.initials: MM
authors.lastname: Bertagnolli
mesh_terms: D000818:Animals; D000068579:Celecoxib; D049109:Cell Proliferation / Q000187:drug effects; D052246:Cyclooxygenase 2 Inhibitors / Q000009:adverse effects*; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism; D005260:Female; D008810:Mice, Inbred C57BL; D018919:Neovascularization, Physiologic / Q000187:drug effects; D011720:Pyrazoles / Q000009:adverse effects*; D013449:Sulfonamides / Q000009:adverse effects*; D014945:Wound Healing / Q000187:drug effects*
chemical_list: D052246:Cyclooxygenase 2 Inhibitors; D011720:Pyrazoles; D013449:Sulfonamides; D000068579:Celecoxib
keywords: Angiogenesis; COX-2; Celecoxib; Myofibroblasts; NSAIDs; PGE(2); Reepithelialization; Wound healing