Kim H J, Abdelkader N, Katz M, McLane J A
Roche Dermatologics, Preclinical Research, Hoffmann-La Roche, Nutley, New Jersey 07110-1199.
J Cell Physiol. 1992 Jun;151(3):579-87. doi: 10.1002/jcp.1041510318.
Both TGF-beta and 1,25-dihydroxy-vitamin-D3 (1,25(OH)2D3) have been reported to decrease the proliferation of normal human keratinocytes. The effect and expression of TGF-beta in keratinocytes treated with 1,25(OH)2D3 was investigated. Human keratinocytes were grown in the presence of various concentrations of TGF-beta and/or 1,25(OH)2D3 prior to enumeration. TGF-beta, alone, has a half maximal dose of inhibition (ED50) of approximately 750 pg/ml after seven days in culture in Keratinocyte Growth Medium (KGM; Clonetics) supplemented with 1.5 mM calcium. When 1,25(OH)2D3 (10(-7)M) was also added to cultures with various concentrations of TGF-beta, the ED50 shifted an average of 2-fold less. The presence of TGF-beta (10 pg/ml) augmented the potency of 1,25(OH)2D3 by at least 10-fold. In keratinocyte cultures, the antiproliferative effect of the two compounds together is synergistic. In keratinocytes grown for 1 week in the presence of 1,25(OH)2D3 at 10(-6)M, the TGF-beta 1 message increased approximately 5-fold. An increase is detected within 2 hours of exposure to 1,25(OH)2D3. There was only a 50% increase in the levels of TGF-beta 2 and no detection of TGF-beta 3. When keratinocyte cultures were treated with 1,25(OH)2D3 and neutralizing antibodies to TGF-beta, the induced-antiproliferative activity was blocked by more than 50%. The keratinocytes produced more active than latent TGF-beta after growth with high doses of 1,25(OH)2D3.
据报道，转化生长因子-β（TGF-β）和1,25-二羟基维生素D3（1,25(OH)2D3）均可降低正常人角质形成细胞的增殖。本研究调查了1,25(OH)2D3处理的角质形成细胞中TGF-β的作用及表达。在计数前，将人角质形成细胞在不同浓度的TGF-β和/或1,25(OH)2D3存在下培养。单独使用TGF-β时，在添加1.5 mM钙的角质形成细胞生长培养基（KGM；Clonetics）中培养7天后，其半数最大抑制剂量（ED50）约为750 pg/ml。当在含有不同浓度TGF-β的培养物中同时加入1,25(OH)2D3（10^(-7)M）时，ED50平均降低约2倍。TGF-β（10 pg/ml）的存在使1,25(OH)2D3的效力增强至少10倍。在角质形成细胞培养物中，这两种化合物的联合抗增殖作用具有协同性。在10^(-6)M的1,25(OH)2D3存在下培养1周的角质形成细胞中，TGF-β1信使核糖核酸增加约5倍。在暴露于1,25(OH)2D3的2小时内即可检测到增加。TGF-β2水平仅增加50%，未检测到TGF-β3。当用1,25(OH)2D3和TGF-β中和抗体处理角质形成细胞培养物时，诱导的抗增殖活性被阻断超过50%。在高剂量1,25(OH)2D3培养后，角质形成细胞产生的活性TGF-β比潜伏性TGF-β更多。
