title: 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.
  
  
  CONCLUSIONS
  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.
authors: Department of Internal Medicine, Division of Nephrology, University Hospital, Zürich, Switzerland. Dialyse-VS.DrWeinreich@T-online.de
authors: T
authors: T
authors: Weinreich
authors: R P
authors: RP
authors: Wüthrich
authors: C
authors: C
authors: Booy
authors: U
authors: U
authors: Binswanger
mesh_terms: D002112:Calcifediol / Q000494:pharmacology; D002117:Calcitriol / Q000494:pharmacology*; D002448:Cell Adhesion / Q000187:drug effects; D002461:Cell Line, Transformed / Q000187:drug effects / Q000378:metabolism; D016895:Culture Media, Serum-Free; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis* / Q000235:genetics; D007371:Interferon-gamma / Q000494:pharmacology; D011994:Recombinant Proteins / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D019010:Vascular Cell Adhesion Molecule-1 / Q000096:biosynthesis / Q000235:genetics
chemical_list: D016895:Culture Media, Serum-Free; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D007371:Interferon-gamma; D002117:Calcitriol; D002112:Calcifediol