
<ArticleTitle>Suppression of <prot>ICAM-1</prot> expression in renal proximal tubular cells by 1,25-dihydroxyvitamin D3.</ArticleTitle>
<AbstractText>Background: 1,25-Dihydroxyvitamin D(3) is mainly synthesized by renal proximal tubular cells. More recently, it has been shown to affect cell growth and <prot>TGF-beta</prot>(1) synthesis in glomerular and tubular renal cells in vitro, and to prevent glomerulosclerosis in vivo in subtotally nephrectomized rats. The mechanisms involved have not been fully identified. We asked whether 1,25-vitamin D(3) might interact with additional immunoregulatory functions of renal cells by studying its effects on the expression of the cellular adhesion molecules <prot>ICAM-1</prot> (<prot>CD54</prot>) and <prot>VCAM-1</prot> (<prot>CD106</prot>) in human proximal tubular cells in vitro (HK-2 cells). Methods: Expression of adhesion molecules was assessed in HK-2 cells cultured under basal conditions and after stimulation with <prot>TNF-alpha</prot> plus <prot>IFN-gamma</prot>, by flow cytometry, gene transcription (RT-PCR) and measurement of soluble <prot>ICAM-1</prot> in culture supernatant by ELISA. Results: Unstimulated HK-2 cells did not express <prot>VCAM-1</prot> and only little <prot>ICAM-1</prot>. 1,25-Vitamin D(3) had no effect on the expression of adhesion molecules in unstimulated cells. TNF/IFN stimulation resulted in a 4-fold increase in <prot>ICAM-1</prot> and <prot>VCAM-1</prot> expression. The TNF/IFN-induced increase in <prot>ICAM-1</prot> expression was reduced by 1,25-vitamin D(3) dose dependently (10(-7) M vs. solvent: -30%; 10(-9) M: -18%; 10(-11) M: -17%). 25(OH)-vitamin D(3) had no effect. <prot>ICAM-1</prot> mRNA concentration was increased in TNF/IFN-stimulated cells. 1,25-Vitamin D(3) treatment prevented the increase of <prot>ICAM-1</prot> mRNA by 27% after 24-72 h incubation (p = 0.03). The TNF/IFN-induced increase in soluble ICAM in culture supernatants was unchanged by 1,25-vitamin D(3). <prot>VCAM-1</prot> expression was unchanged by incubation with 1,25-vitamin D(3) under basal conditions and after TNF/IFN stimulation. Conclusion: 1,25-Vitamin D(3) inhibits cytokine-induced <prot>ICAM-1</prot> but not <prot>VCAM-1</prot> expression in renal proximal tubular cells in vitro. The present data support the hypothesis that 1,25-vitamin D(3) is not only synthesized by renal tubular cells, but may also affect immunoregulatory functions in these cells.</AbstractText>
