Department of Nephrology, The First Affiliated Hospital, China Medical University, Shenyang, Liaoning, PR China.
Cell Immunol. 2011;271(1):173-9. doi: 10.1016/j.cellimm.2011.06.017. Epub 2011 Jul 2.
1,25(OH)(2)D(3), the active metabolite of vitamin D(3), its activity is not limited to mineral and skeletal homeostasis. In recent years, there has been increasing evidence pointing to the role of its activity in the regulation of cell proliferation, cell differentiation and immunomodulation. Here we report lipopolysaccharide (LPS), a glycolipid that is produced and secreted by gram-negative bacteria during peritonitis, plus high glucose (HG) can significantly inhibit mesothelial cell viability while induce more apoptosis in rat peritoneal mesothelial cells (RPMC). Pretreatment with 1,25(OH)(2)D(3) can reverse the above effect in a concentration dependent manner. HG plus LPS can down-regulate the levels of both mRNA and protein of VDR, and up-regulate the expression of TGF-β1 and TNF-α in RPMC, which can also be effectively reversed by pretreatment with 1,25(OH)(2)D(3). The above results suggest that HG plus LPS may induce changes in RPMC's viability and apoptosis, leading to peritoneal injury. 1,25(OH)(2)D(3) can reverse the inhibition of cell viability, the increase of apoptotic rate and induction of fibrosis related cytokine TGF-β1 and TNF-α by HG plus LPS in RPMC, thus protect peritoneal membrane.
1,25(OH)(2)D(3),维生素 D(3)的活性代谢物,其作用不仅局限于矿物质和骨骼的稳态调节。近年来,越来越多的证据表明其活性在细胞增殖、细胞分化和免疫调节中的作用。本文报道了脂多糖(LPS),一种革兰氏阴性菌在腹膜炎期间产生和分泌的糖脂,加上高葡萄糖(HG)可显著抑制大鼠腹膜间皮细胞(RPMC)活力,同时诱导更多的细胞凋亡。1,25(OH)(2)D(3)预处理可呈浓度依赖性逆转上述作用。HG 加 LPS 可下调 RPMC 中 VDR 的 mRNA 和蛋白水平,并上调 TGF-β1 和 TNF-α的表达,1,25(OH)(2)D(3)预处理也可有效逆转上述作用。上述结果表明,HG 加 LPS 可能导致 RPMC 活力和凋亡发生变化,导致腹膜损伤。1,25(OH)(2)D(3)可逆转 HG 加 LPS 诱导的 RPMC 活力抑制、凋亡率增加和纤维化相关细胞因子 TGF-β1 和 TNF-α的诱导,从而保护腹膜。