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Suppression of ICAM-1 expression in renal proximal tubular cells by 1,25-dihydroxyvitamin D3.

Abstract：

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 TGF-beta(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 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-alpha plus IFN-gamma, 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 D(3) 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 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. ICAM-1 mRNA concentration was increased in TNF/IFN-stimulated cells. 1,25-Vitamin D(3) 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 D(3). VCAM-1 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 ICAM-1 but not VCAM-1 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.

journal_name

Kidney Blood Press Res

journal_title

Kidney & blood pressure research

authors

Weinreich T,Wüthrich RP,Booy C,Binswanger U

doi

10.1159/000054213

keywords:

subject

Has Abstract

pub_date

2001-01-01 00:00:00

pages

92-8

issue

eissn

1420-4096

issn

1423-0143

pii

54213

journal_volume

pub_type

杂志文章

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Suppression of ICAM-1 expression in renal proximal tubular cells by 1,25-dihydroxyvitamin D3.