Sphingosine 1-phosphate is involved in cytoprotective actions of calcitriol in human fibroblasts and enhances the intracellular Bcl-2/Bax rheostat.

摘要: Calcitriol is originally known to decrease proliferation rates of several carcinoma cells, partly via induction apoptosis. On the other hand, secosteroid revealed protect some cell types like thyrocytes, HL-60 cells and melanocytes against programmed death. Here we report that calcitriol despite its strong antiproliferative effect on human dermal fibroblasts did not induce apoptosis in these cells. In contrast, possessed an antiapoptotic action fibroblasts. Thus, ability apoptotic stimuli TNFalpha/actinomycin C2-ceramides (C2-Cer) death was drastically diminished presence calcitriol. Moreover, identified sphingosine 1-phosphate (S1P) as a downstream mediator for cytoprotective property. could from N,N-dimethylsphingosine (DMS), which inhibits kinase, crucial enzyme form S1P. Like calcitriol, S1P different concentrations fibroblast moreover decreased after treatment with TNFalpha1/actinomycin. As has been modify Bcl-2/ Bax ratio epithelial keratinocytes, also measured expression proteins revealing increased Bcl-2 level stimulation while protein modified. conclusion, H by formation resulting changed Bcl-2/Bax ratio.