Zouboulis C C, Korge B P, Mischke D, Orfanos C E
Department of Dermatology, University Medical Center Steglitz, Germany.
J Invest Dermatol. 1993 Oct;101(4):628-33. doi: 10.1111/1523-1747.ep12366092.
Human sebocytes maintained in medium containing delipidized serum were studied for ultrastructural characteristics, cell proliferation, lipid synthesis, immunophenotype, and keratin expression before and after the addition of the synthetic retinoids isotretinoin and acitretin (10(-8)-10(-5) M). Compared to the properties of sebocytes cultured in normal sebocyte medium (1-2 x 10(-7) M vitamin A), the use of delipidized serum (undetectable amounts of vitamin A) resulted in prominent decrease of i) proliferation; ii) number of intracellular lipid droplets and synthesis of total lipids, especially triglycerides, squalene, and wax esters; and iii) labeling with monoclonal antibodies identifying progressive and late-stage sebocyte differentiation. Intercellular spaces narrowed and cell-to-cell contacts were established by abundant desmosomes. Lanosterol was induced. Keratins 14, 16, 17, and 18 were upregulated and the keratin 16: keratin 4 ratio, negatively correlating with sebocyte differentiation, increased. Addition of isotretinoin and acitretin exerted a biphasic effect. At concentrations < or = 10(-7) M, both compounds enhanced sebocyte proliferation and synthesis of total lipids, especially triglycerides and cholesterol, and decreased lanosterol, keratin 16, and the keratin 16:keratin 4 ratio. In contrast, retinoid concentrations > 10(-7) M inhibited sebocyte proliferation in a dose-dependent manner. Our findings indicate that vitamin A is essential for proliferation, synthetic activity, and differentiation of human sebocytes in vitro. Synthetic retinoids partially reinstate the altered functions of sebocytes maintained in medium containing delipidized serum. In contrast to the previously shown isotretinoin-specific response of cultured sebocytes in the presence of vitamin A, similar effects of isotretinoin and acitretin were obtained in its absence. This suggests different interactions of synthetic retinoids with vitamin A, possibly influencing their efficacy on the sebaceous gland.
研究了在含有去脂血清的培养基中培养的人皮脂腺细胞，观察其在添加合成维甲酸异维甲酸和阿维A（10^(-8)-10^(-5)M）前后的超微结构特征、细胞增殖、脂质合成、免疫表型和角蛋白表达。与在正常皮脂腺细胞培养基（1-2×10^(-7)M维生素A）中培养的皮脂腺细胞特性相比，使用去脂血清（维生素A含量不可检测）导致以下情况显著降低：i）增殖；ii）细胞内脂质小滴数量和总脂质合成，尤其是甘油三酯、角鲨烯和蜡酯；iii）用识别进展期和晚期皮脂腺细胞分化的单克隆抗体标记。细胞间隙变窄，通过丰富的桥粒建立细胞间接触。羊毛甾醇被诱导。角蛋白14、16、17和18上调，与皮脂腺细胞分化呈负相关的角蛋白16:角蛋白4比值增加。添加异维甲酸和阿维A产生双相效应。在浓度≤10^(-7)M时，两种化合物均增强皮脂腺细胞增殖和总脂质合成，尤其是甘油三酯和胆固醇，并降低羊毛甾醇、角蛋白16和角蛋白16:角蛋白4比值。相反，维甲酸浓度>10^(-7)M以剂量依赖方式抑制皮脂腺细胞增殖。我们的研究结果表明，维生素A对于体外人皮脂腺细胞的增殖、合成活性和分化至关重要。合成维甲酸部分恢复了在含有去脂血清的培养基中培养的皮脂腺细胞改变的功能。与之前在维生素A存在下培养的皮脂腺细胞显示的异维甲酸特异性反应相反，在其不存在时获得了异维甲酸和阿维A的类似效果。这表明合成维甲酸与维生素A有不同的相互作用，可能影响它们对皮脂腺的功效。
