Cyclooxygenases in human and mouse skin and cultured human keratinocytes: Association of COX-2 expression with human keratinocyte differentiation
Cyclooxygenases in human and mouse skin and cultured human keratinocytes: Association of COX-2 expression with human keratinocyte differentiation
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DOI：
10.1006/excr.1996.0113
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发表时间：
1996-04-10
影响因子：
3.7
通讯作者：
Goldyne, ME
中科院分区：
文献类型：
--
作者：
Leong, J;HughesFulford, M;Goldyne, ME
用人和小鼠皮肤活检切片的免疫组织化学方法和培养的人新生包皮角质形成细胞蛋白提取液的Western blotting方法检测两种前列腺素H环氧合酶亚型(COX-1和COX-2)在表皮中的表达。在正常人皮肤中，环氧合酶-1免疫染色贯穿整个表皮，而环氧合酶-2免疫染色在分化程度较高的基底上角质形成细胞中增加。基底细胞癌几乎不表达环氧合酶-1或环氧合酶-2，而这两种同工酶在鳞状细胞癌中都有很强的表达，这两种同工酶起源于更分化的表皮层。在培养的人角质形成细胞中，提高细胞外钙离子浓度(公认的角质形成细胞分化刺激因素)会导致COX-2蛋白和mRNA表达增加，而COX-1蛋白的表达对钙的反应没有明显变化。由于最近的一份报告未能在正常小鼠的表皮中显示COX-2，我们也在正常和丙酮处理的小鼠皮肤切片中观察了COX-1和COX-2的免疫染色。与以前的报道一致，在正常小鼠的表皮中发现了一些COX-1，但没有COX-2的免疫染色。然而，在丙酮处理后，COX-1的表达显著增加，并且在基底层出现了显著的COX-2免疫染色。这些结果表明，COX-2在人表皮和人角质形成细胞培养中的表达是正常角质形成细胞分化的一部分，而在小鼠表皮中，COX-2的组成性表达是不存在的，但如先前报道的那样是可以诱导的。(C)1996年学术出版社。
Epidermal expression of the two isoforms of the prostaglandin H-generating cyclooxygenase (COX-1 and COX-2) was evaluated both by immunohistochemistry performed on human and mouse skin biopsy sections and by Western blotting of protein extracts from cultured human neonatal foreskin keratinocytes. In normal human skin, COX-1 immunostaining is observed throughout the epidermis whereas COX-2 immunostaining increases in the more differentiated, suprabasilar keratinocytes. Basal cell carcinomas express little if any COX-1 or COX-2 immunostaining whereas both isozymes are strongly expressed in squamous cell carcinomas deriving from a more differentiated layer of the epidermis. In human keratinocyte cultures, raising the extracellular calcium concentration, a recognized stimulus for keratinocyte differentiation, leads to an increased expression of both COX-2 protein and mRNA; expression of COX-1 protein, however, shows no significant alteration in response to calcium. Because of a recent report that failed to show COX-2 in normal mouse epidermis, we also looked for COX-1 and COX-2 immunostaining in sections of normal and acetone-treated mouse skin. In agreement with a previous report, some COX-1, but no COX-2, immunostaining is seen in normal murine epidermis. However, following acetone treatment, there is a marked increase in COX-1 expression as well as the appearance of significant COX-2 immunostaining in the basal layer. These data suggest that in human epidermis as well as in human keratinocyte cultures, the expression of COX-2 occurs as a part of normal keratinocyte differentiation whereas in murine epidermis, its constitutive expression is absent, but inducible as previously published. (C) 1996 Academic Press, Inc.