UVB-irradiated keratinocytes induce melanoma-associated ganglioside GD3 synthase gene in melanocytes via secretion of tumor necrosis factor α and interleukin 6.
UVB-irradiated keratinocytes induce melanoma-associated ganglioside GD3 synthase gene in melanocytes via secretion of tumor necrosis factor α and interleukin 6.
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UVB 照射的角质形成细胞通过分泌肿瘤坏死因子 α 和白细胞介素 6，在黑素细胞中诱导黑色素瘤相关神经节苷脂 GD3 合酶基因。
DOI：
10.1016/j.bbrc.2014.02.038
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发表时间：
2014
期刊：
影响因子：
--
通讯作者：
Miyata M.
中科院分区：
文献类型：
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作者：
青柳共太;今泉美佳;西脇知世乃;中道洋子;永松信哉;Miyata M.
虽然神经节苷脂及其合成酶基因在恶性黑色素瘤中的表达已得到很好的研究，但在正常黑素细胞中的表达却很少分析。特别是，糖基转移酶基因的表达水平的变化，负责神经节苷脂合成的黑色素瘤从黑色素细胞的演变过程中是非常重要的，以了解神经节苷脂在黑色素瘤中的作用。在这里，糖基转移酶基因的表达相关的神经节苷脂的合成进行了分析，使用RNA从培养的黑素细胞和黑色素瘤细胞系。定量RT-PCR显示，与黑素细胞相比，黑色素瘤表达高水平的GD 3合酶和GM 2/GD 2合酶基因mRNA，而GM 1/GD 1b合酶基因表达低水平。以紫外线B（UVB）为代表，分析了UVB对黑素细胞3种主要神经节苷脂合成酶基因表达水平的影响。虽然直接UVB照射的黑素细胞没有引起显着的变化，UVB照射的角质形成细胞（HaCaT细胞）的培养上清液诱导明确的上调GD 3合酶和GM 2/GD 2合酶基因。对上清液的详细检查显示，炎性细胞因子如TNFα和IL-6增强GD 3合酶基因表达。这些结果表明，炎症细胞因子分泌的UVB照射的角质形成细胞诱导黑色素瘤相关的神经节苷脂合成酶基因，提出皮肤微环境中的黑色素瘤样神经节苷脂在黑色素细胞中的促进作用。
Although expression of gangliosides and their synthetic enzyme genes in malignant melanomas has been well studied, that in normal melanocytes has been scarcely analyzed. In particular, changes in expression levels of glycosyltransferase genes responsible for ganglioside synthesis during evolution of melanomas from melanocytes are very important to understand roles of gangliosides in melanomas. Here, expression of glycosyltransferase genes related to the ganglioside synthesis was analyzed using RNAs from cultured melanocytes and melanoma cell lines. Quantitative RT-PCR revealed that melanomas expressed high levels of mRNA of GD3 synthase and GM2/GD2 synthase genes and low levels of GM1/GD1b synthase genes compared with melanocytes. As a representative exogenous stimulation, effects of ultraviolet B (UVB) on the expression levels of 3 major ganglioside synthase genes in melanocytes were analyzed. Although direct UVB irradiation of melanocytes caused no marked changes, culture supernatants of UVB-irradiated keratinocytes (HaCaT cells) induced definite up-regulation of GD3 synthase and GM2/GD2 synthase genes. Detailed examination of the supernatants revealed that inflammatory cytokines such as TNFα and IL-6 enhanced GD3 synthase gene expression. These results suggest that inflammatory cytokines secreted from UVB-irradiated keratinocytes induced melanoma-associated ganglioside synthase genes, proposing roles of skin microenvironment in the promotion of melanoma-like ganglioside profiles in melanocytes.