The role of the epidermal endothelin cascade in the hyperpigmentation mechanism of lentigo senilis
The role of the epidermal endothelin cascade in the hyperpigmentation mechanism of lentigo senilis
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DOI：
10.1046/j.1523-1747.2001.01296.x
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发表时间：
2001-04-01
影响因子：
6.5
通讯作者：
Imokawa, G
中科院分区：
文献类型：
--
作者：
Kadono, S;Manaka, I;Imokawa, G
关于老年雀斑色素沉着过度的机制知之甚少。我们之前报道过，角质形成细胞衍生的内皮素是人类黑素细胞内在的旁分泌丝裂原和黑素原，并且它们在刺激紫外线 B 诱导的黑素生成中发挥重要作用。在这项研究中，我们使用免疫组织化学和逆转录聚合酶链反应分析来阐明内皮素级联反应，包括内皮素的产生、内皮素转换酶的加工和内皮素B受体的表达，在老年性雀斑样色素沉着机制中的作用，老年雀斑样病变皮肤中酪氨酸酶免疫阳性黑素细胞的数量比病变周围增加了2倍。表皮。使用内皮素-1抗体进行的免疫组织化学显示，病灶表皮中的染色比病灶周围表皮的染色相对更强，同时逆转录酶聚合酶链反应分析表明，老年雀斑样痣病灶皮肤中内皮素-1和内皮素B受体转录物的表达增强，同时与病灶周围对照相比，酪氨酸酶mRNA的表达也类似增强。通过转录水平和免疫染色测定，内皮素 1 诱导细胞因子肿瘤坏死因子 α 在老年雀斑样病变表皮中持续上调，而白细胞介素 1 α 下调。相反，病变表皮中内皮素转换酶 1 α mRNA 并未显着增加。这些发现表明，表皮内皮素级联的增强，尤其是内皮素和内皮素 B 受体表达的增强，在老年雀斑色素沉着过度的机制中发挥着重要作用。
Little is known about the mechanism(s) underlying hyperpigmentation in lentigo senilis. We have previously reported that keratinocyte-derived endothelins are intrinsic paracrine mitogens and melanogens for human melanocytes and that they play an essential role in stimulating ultraviolet-B-induced melanogenesis. In this study, we have used immunohistochemistry and reverse transcriptase polymerase chain reaction analysis to clarify the role of the endothelin cascade, including endothelin production, processing by endothelin-converting enzyme, and expression of the endothelin B receptor, in the hyperpigmentary mechanism(s) involved in lentigo senilis, The number of tyrosinase immunopositive melanocytes in lentigo senilis lesional skin was increased 2-fold over the perilesional epidermis. Immunohistochemistry using antibodies to endothelin-1 demonstrated relatively stronger staining in the lesional epidermis than in the perilesional epidermis, Reverse transcriptase polymerase chain reaction analysis concomitantly demonstrated accentuated expression of transcripts for endothelin-1 and for the endothelin B receptor in lentigo senilis lesional skin, which was accompanied by a similar accentuated expression of tyrosinase mRNA compared with the perilesional control. The endothelin-1-inducible cytokine, tumor necrosis factor alpha, was consistently upregulated in the lentigo senilis lesional epidermis as determined at the transcriptional level and by immunostaining, whereas interleukin-1 alpha was downregulated, In contrast, endothelin-converting enzyme 1 alpha mRNA was not substantially increased in the lesional epidermis. These findings suggest that an accentuation of the epidermal endothelin cascade, especially with respect to expression of endothelin and the endothelin B receptor, plays an important role in the mechanism involved in the hyperpigmentation of lentigo senilis.