Lehmann Bodo, Abraham Susanne, Meurer Michael
Department of Dermatology, Carl Gustav Carus Medical School, Dresden University of Technology, Dresden D-01307, Germany.
J Steroid Biochem Mol Biol. 2004 May;89-90(1-5):561-5. doi: 10.1016/j.jsbmb.2004.03.071.
UVB irradiation of cultured human keratinocytes induces both the conversion of 7-dehydrocholesterol (7-DHC) to calcitriol (1alpha,25(OH)(2)D(3)) and the release of tumor necrosis factor-alpha (TNF-alpha) in these cells. Calcitriol synthesis in human keratinocytes was reduced in the presence if a neutralizing polyclonal antibody directed against human TNF-alpha. On the other hand, we found a 1.7-fold higher stimulatory effect of UVB on liberation of TNF-alpha in cultured keratinocytes enriched with 7-DHC compared with irradiated cell cultures in absence of 7-DHC. These observations argue in favor of a synergetic relationship between generation of TNF-alpha and calcitriol in UVB irradiated keratinocytes. In addition, we found that TNF-alpha potently increases the conversion rate of Vitamin D(3) (cholecalciferol) to calcitriol in this cell system. The UVB-triggered formation of both TNF-alpha and calcitriol in cultured keratinocytes was wavelength-, time- and dose-dependent. Maximum formation of TNF-alpha and calcitriol was found at 300 nm and UVB doses of 30 mJ/cm2. The enhancement of both the formation of TNF-alpha and calcitriol in keratinocytes by UVB may be of relevance for regulation of growth and apoptosis in light-exposed epidermal cells and, in addition, may play a role in the UVB treatment of diseased skin including psoriasis.
对培养的人角质形成细胞进行紫外线B（UVB）照射，可诱导这些细胞中7-脱氢胆固醇（7-DHC）转化为骨化三醇（1α,25(OH)₂D₃），并释放肿瘤坏死因子-α（TNF-α）。如果存在针对人TNF-α的中和多克隆抗体，人角质形成细胞中的骨化三醇合成会减少。另一方面，我们发现，与不含7-DHC的照射细胞培养物相比，富含7-DHC的培养角质形成细胞中，UVB对TNF-α释放的刺激作用高1.7倍。这些观察结果支持UVB照射的角质形成细胞中TNF-α生成与骨化三醇之间存在协同关系。此外，我们发现TNF-α能显著提高该细胞系统中维生素D₃（胆钙化醇）向骨化三醇的转化率。培养的角质形成细胞中UVB触发的TNF-α和骨化三醇的形成具有波长、时间和剂量依赖性。在300nm波长和30mJ/cm²的UVB剂量下，TNF-α和骨化三醇的形成达到最大值。UVB对角质形成细胞中TNF-α和骨化三醇形成的增强作用，可能与光照表皮细胞的生长和凋亡调节有关，此外，可能在包括银屑病在内的患病皮肤的UVB治疗中发挥作用。
