Müller-Decker Karin, Hirschner Wolfgang, Marks Friedrich, Fürstenberger Gerhard
Deutsches Krebsforschungszentrum, Research Program Tumor Cell Regulation, Im Neuenheimer Feld 280, D-69120 Heidelberg, Germany.
J Invest Dermatol. 2002 Nov;119(5):1189-95. doi: 10.1046/j.1523-1747.2002.19501.x.
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.
除了具有促炎活性外，前列腺素最近还被证明在组织损伤和炎症的消退中具有益处。因此，在这些情况下抑制环氧化酶-2（主要的前列腺素内过氧化物合酶），可能不仅会导致炎症反应减弱，还会延迟组织再生和修复。为此，我们研究了环氧化酶同工酶的表达以及环氧化酶抑制剂对小鼠皮肤全层切口伤口愈合的影响。免疫组织化学分析显示，在增生上皮的角质形成细胞中环氧化酶同工酶有显著表达，环氧化酶-1免疫信号在上基底层占主导，而环氧化酶-2免疫信号遍布整个表皮。此外还发现，类似朗格汉斯细胞的树突状细胞以及肉芽组织附近或内部的内皮细胞和巨噬细胞均表达这两种同工酶。口服环氧化酶-1选择性抑制剂SC-560或环氧化酶-2选择性抑制剂伐地考昔抑制前列腺素E2合成，在宏观上并未延缓小鼠皮肤伤口愈合。除了在伤口诱导的新生血管形成早期上皮化有轻微短暂延迟外，这些药物并未延迟胶原沉积和抗张强度的恢复。同样，非选择性抑制剂吲哚美辛对切口皮肤伤口的抗张强度也没有影响。
