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>1,25‐dihydroxy‐vitamin‐D3enhances antiproliferative effect and transcription of TGF‐β1 on human keratinocytes in culture
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1,25‐dihydroxy‐vitamin‐D3enhances antiproliferative effect and transcription of TGF‐β1 on human keratinocytes in culture
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机译：1,25‐dihydroxy‐vitamin‐D3enhances antiproliferative effect and transcription of TGF‐β1 on human keratinocytes in culture
AbstractBoth TGF‐β 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‐β in keratinocytes treated with 1,25(OH)2D3was investigated. Human keratinocytes were grown in the presence of various concentrations of TGF‐β and/or 1,25(OH)2D3prior to enumeration. TGF‐β, 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(10−7M) was also added to cultures with various concentrations of TGF‐β, the ED50shifted an average of 2‐fold less. The presence of TGF‐β (10 pg/ml) augmented the potency of 1,25(OH)2D3by 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)2D3at 10−6M, the TGF‐β1 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‐β2 and no detection of TGF‐β3. When keratinocyte cultures were treated with 1,25(OH)2D3and neutralizing antibodies to TGF‐β, the induced‐antiproliferative activity was blocked by more than 50. The keratinocytes produced more active than latent TGF‐β after growth wit
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