title: The effects of cyclooxygenase isozyme inhibition on incisional wound healing in mouse skin.
abstract: In addition to their proinflammatory activities, prostaglandins recently have been shown to be beneficial in the resolution of tissue injury and inflammation. Thus, inhibition of cyclooxygenase-2, the predominant prostaglandin endoperoxide synthase under these conditions, may not only result in attenuating the inflammatory response but also in delaying tissue regeneration and repair. To this end, we investigated cyclooxygenase isozyme expression and the effects of cyclooxygenase inhibitors on wound healing upon full-thickness incisions in mouse skin. Immunohistochemical analysis revealed prominent expression of cyclooxygenase isozymes in keratinocytes of the hyperplastic epithelium, with cyclooxygenase-1 immunosignals predominating in the suprabasal compartment and cyclooxygenase-2 immunosignals spread throughout the whole epidermis. Moreover, dendritic cells, resembling Langerhans cells, as well as endothelial cells and macrophages in the vicinity of or within the granulation tissue were found to express both isozymes. Inhibition of prostaglandin E2 synthesis by oral administration of the cyclooxygenase-1-selective inhibitor SC-560 or the cyclooxygenase-2-selective inhibitor valdecoxib did not retard wound healing in mouse skin macroscopically. Except for a slight transient retardation of epithelialization early after wounding wound-induced neoangiogenesis, collagen deposition, and the restoration of tensile strength were not delayed by these agents. Likewise, the nonselective inhibitor indomethacin had no effect on the tensile strength of incisional skin wounds.
authors.affiliation: Deutsches Krebsforschungszentrum, Research Program Tumor Cell Regulation, Im Neuenheimer Feld 280, D-69120 Heidelberg, Germany. K.Mueller-Decker@dkfz.de
authors.forename: Karin
authors.initials: K
authors.lastname: Müller-Decker
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Hirschner
authors.forename: Friedrich
authors.initials: F
authors.lastname: Marks
authors.forename: Gerhard
authors.initials: G
authors.lastname: Fürstenberger
mesh_terms: D000208:Acute Disease; D000818:Animals; D003094:Collagen / Q000378:metabolism; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D004195:Disease Models, Animal; D005260:Female; D007527:Isoenzymes / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000378:metabolism; D007555:Isoxazoles / Q000494:pharmacology*; D051379:Mice; D008815:Mice, Inbred Strains; D018919:Neovascularization, Physiologic / Q000187:drug effects; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis / Q000378:metabolism; D011720:Pyrazoles / Q000494:pharmacology; D012867:Skin / Q000201:enzymology* / Q000293:injuries; D013449:Sulfonamides / Q000494:pharmacology*; D013718:Tensile Strength / Q000187:drug effects; D014945:Wound Healing / Q000187:drug effects* / Q000502:physiology; D000096926:Benzenesulfonamides
chemical_list: D003094:Collagen; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D007555:Isoxazoles; D011451:Prostaglandin-Endoperoxide Synthases; D011720:Pyrazoles; D013449:Sulfonamides; C115461:SC 560; C406224:valdecoxib; D000096926:Benzenesulfonamides