Kitamura Reiko, Tsukamoto Katsuhiko, Harada Kazutoshi, Shimizu Akira, Shimada Shinji, Kobayashi Takeshi, Imokawa Genji
Department of Dermatology, University of Yamanashi, Faculty of Medicine, Yamanashi, Japan.
J Pathol. 2004 Apr;202(4):463-75. doi: 10.1002/path.1538.
Little is known about the mechanisms involved in the dysfunction of melanocytes in vitiligo epidermis. It is hypothesized that some cytokine/receptor interactions may be affected, resulting in dysfunction and/or loss of melanocytes. This study has compared the expression of endothelin (ET)-1, the ET-1 receptor (ET(B)R), granulocyte macrophage colony stimulating factor (GM-CSF), stem cell factor (SCF), the SCF receptor (KIT protein), tyrosinase, and S100 alpha between lesional and non-lesional vitiligo epidermis. Analysis by reverse transcription-polymerase chain reaction (RT-PCR) and by western blotting for ET-1 and SCF unexpectedly demonstrated up-regulated expression of these cytokines in lesional vitiligo epidermis. Immunohistochemistry with antibodies to melanocyte markers revealed that at the edge of the lesional epidermis, melanocytes remain and express tyrosinase, S100 alpha and ET(B)R, but not KIT protein or melanocyte-specific microphthalmia-associated transcription factor (MITF-M). Quantitation of the staining revealed a slight or moderate decrease in the number of S100 alpha, tyrosinase, and ET(B)R-positive cells at the edge of the lesional epidermis. In contrast, the number of cells expressing KIT protein was markedly decreased at the edge of the lesional epidermis compared with the non-lesional epidermis. At the centre of the lesional epidermis, there was complete loss of melanocytes expressing KIT protein, S100 alpha, ET(B)R, and/or tyrosinase. Western blotting revealed down-regulated expression of c-kit and MITF-M proteins at the edge of the lesional epidermis in vitiligo. These findings suggest that reduction in the expression of KIT protein by melanocytes and its downstream effectors, including MITF-M, may be associated with the dysfunction and/or loss of melanocytes in vitiligo epidermis.
关于白癜风表皮中黑素细胞功能障碍所涉及的机制，目前了解甚少。据推测，某些细胞因子/受体相互作用可能受到影响，从而导致黑素细胞功能障碍和/或丧失。本研究比较了内皮素（ET）-1、ET-1受体（ET(B)R）、粒细胞巨噬细胞集落刺激因子（GM-CSF）、干细胞因子（SCF）、SCF受体（KIT蛋白）、酪氨酸酶和S100α在白癜风皮损区和非皮损区表皮中的表达。通过逆转录聚合酶链反应（RT-PCR）以及对ET-1和SCF进行蛋白质印迹分析，意外地发现这些细胞因子在白癜风皮损区表皮中的表达上调。用黑素细胞标志物抗体进行免疫组织化学分析显示，在皮损区表皮边缘，黑素细胞仍然存在并表达酪氨酸酶、S100α和ET(B)R，但不表达KIT蛋白或黑素细胞特异性小眼相关转录因子（MITF-M）。对染色进行定量分析发现，皮损区表皮边缘S100α、酪氨酸酶和ET(B)R阳性细胞数量略有或中度减少。相比之下，与非皮损区表皮相比，皮损区表皮边缘表达KIT蛋白的细胞数量明显减少。在皮损区表皮中心，表达KIT蛋白、S100α、ET(B)R和/或酪氨酸酶的黑素细胞完全缺失。蛋白质印迹分析显示，白癜风皮损区表皮边缘c-kit和MITF-M蛋白的表达下调。这些发现表明，黑素细胞及其下游效应因子（包括MITF-M）中KIT蛋白表达的降低可能与白癜风表皮中黑素细胞的功能障碍和/或丧失有关。
