Suppression of ICAM-1 expression in renal proximal tubular cells by 1,25-dihydroxyvitamin D-3

Background: 1,25-Dihydroxyvitamin Dg is mainly synthesized by renal proxima l tubular cells. More recently, it has been shown to affect cell growth and TGF-beta (1) synthesis in glomerular and tubular renal cells in vitro, and to prevent glomerulosclerosis in vivo in subtotally nephrectomized rats. T he mechanisms involved have not been fully identified. We asked whether 1,2 5-vitamin D-3 might interact with additional immunoregulatory functions of renal cells by studying its effects on the expression of the cellular adhes ion molecules ICAM-1 (CD54) and VCAM-1 (CD106) in human proximal tubular ce lls in vitro (HK-2 cells). Methods: Expression of adhesion molecules was as sessed in HK-2 cells cultured under basal conditions and after stimulation with TNF-alpha plus IFN-gamma, by flow cytometry, gene transcription (RT-PC R) and measurement of soluble ICAM-1 in culture supernatant by ELISA. Resul ts: Unstimulated HK-2 cells did not express VCAM-1 and only little ICAM-1. 1,25-Vitamin D-3 had no effect on the expression of adhesion molecules in u nstimulated cells. TNF/IFN stimulation resulted in a 4-fold increase in ICA M-1 and VCAM-1 expression. The TNF/IFN-induced increase in ICAM-1 expressio n was reduced by 1,25-vitamin D-3 dose dependently (10(-7) Mvs. solvent: -3 0%; 10(-9) M: -18%; 10(-11) M: -17%). 25(OH)-vitamin D-3 had no effect. ICA M-1 mRNA concentration was increased in TNF/IFN-stimulated cells. 1,25-Vita min Dg treatment prevented the increase of ICAM-1 mRNA by 27% after 24-72 h incubation (p = 0.03). The TNF/IFN-induced increase in soluble ICAM in cul ture supernatants was unchanged by 1,25-vitamin D-3 VCAM-1 expression was u nchanged by incubation with 1,25-vitamin D-3 under basal conditions and aft er TNF/IFN stimulation. Conclusion: 1,25-Vitamin D-3 inhibits cytokine-indu ced ICAM-1 but not VCAM-1 expression in renal proximal tubular cells in vit ro. The present data support the hypothesis that 1,25-vitamin Dg is not onl y synthesized by renal tubular cells, but may also affect immunoregulatory functions in these cells. Copyright (C) 2001 S. Karger AG. Basel.