Suppression of ICAM-1 Expression in Renal Proximal Tubular Cells by 1,25-Dihydroxyvitamin D3

Abstract

Background: 1,25-Dihydroxyvitamin D₃ is mainly synthesized by renal proximal tubular cells. More recently, it has been shown to affect cell growth and TGF-β₁ 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 D₃ might interact with additional immunoregulatory functions of renal cells by studying its effects on the expression of the cellular adhesion molecules ICAM-1 (CD54) and VCAM-1 (CD106) 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 TNF-α plus IFN-γ, by flow cytometry, gene transcription (RT-PCR) and measurement of soluble ICAM-1 in culture supernatant by ELISA. Results: Unstimulated HK-2 cells did not express VCAM-1 and only little ICAM-1. 1,25-Vitamin D₃ had no effect on the expression of adhesion molecules in unstimulated cells. TNF/IFN stimulation resulted in a 4-fold increase in ICAM-1 and VCAM-1 expression. The TNF/IFN-induced increase in ICAM-1 expression was reduced by 1,25-vitamin D₃ dose dependently (10^–7 M vs. solvent: –30%; 10^–9 M: –18%; 10^–11 M: –17%). 25(OH)-vitamin D₃ had no effect. ICAM-1 mRNA concentration was increased in TNF/IFN-stimulated cells. 1,25-Vitamin D₃ 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 culture supernatants was unchanged by 1,25-vitamin D₃. VCAM-1 expression was unchanged by incubation with 1,25-vitamin D₃ under basal conditions and after TNF/IFN stimulation. Conclusion: 1,25-Vitamin D₃ inhibits cytokine-induced ICAM-1 but not VCAM-1 expression in renal proximal tubular cells in vitro. The present data support the hypothesis that 1,25-vitamin D₃ is not only synthesized by renal tubular cells, but may also affect immunoregulatory functions in these cells.