title: 1,25-Dihydroxyvitamin D3 upregulates functional C-x-C chemokine receptor type 4 expression in human eosinophils.
abstract: BACKGROUND
  Epidemiological studies suggest that vitamin D may be protective against the inception and exacerbation of allergic diseases. However, the direct effect of vitamin D on eosinophils, the major effector cells in allergic inflammation, is not known. It has been reported that C-X-C chemokine receptor type 4 (CXCR4) in eosinophils is induced in non-Th2 cytokine milieu or in response to glucocorticoids, recruiting the cell to noninflammatory sites.
  
  
  OBJECTIVE
  To test whether 1,25-dihydroxyvitamin D(3) [1,25-(OH)(2)D(3) or calcitriol], the active metabolite of vitamin D, acts directly on eosinophils to induce upregulation of CXCR4.
  
  
  METHODS
  Peripheral blood eosinophils from normal volunteers were isolated by CD16 immunomagnetic beads. Vitamin D receptor (VDR) expression was detected by RT-PCR. Eosinophils were cultured with 1,25-(OH)(2)D(3) and the survival and expression of CXCR4 on eosinophils were measured by flowcytometry. Eosinophil migration by CXCL-12/SDF-1 in the presence of 1,25-(OH)(2)D(3) was also analyzed.
  
  
  RESULTS
  Eosinophils expressed VDR. 1,25-(OH)(2)D(3) prolonged eosinophil survival and upregulated eosinophil surface expression of CXCR4 in a concentration-dependent manner. Interleukin (IL)-5 significantly reduced CXCR4 expression and migration induced by the ligand CXCL-12/SDF-1. 1,25-(OH)(2)D(3) reversed the negative effects of IL-5 on the CXCR4-CXCL12 pathway.
  
  
  CONCLUSIONS
  1,25-(OH)(2)D(3) regulates CXCR4 expression in eosinophils. The mechanism may be involved in eosinophil recruitment to noninflammatory sites where the ligand of CXCR4 is constitutively expressed.
authors.affiliation: Institute for Clinical Research, Mie National Hospital, Tsu, Japan.
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Hiraguchi
authors.forename: Hisashi
authors.initials: H
authors.lastname: Tanida
authors.forename: Mayumi
authors.initials: M
authors.lastname: Sugimoto
authors.forename: Koa
authors.initials: K
authors.lastname: Hosoki
authors.forename: Mizuho
authors.initials: M
authors.lastname: Nagao
authors.forename: Reiko
authors.initials: R
authors.lastname: Tokuda
authors.forename: Takao
authors.initials: T
authors.lastname: Fujisawa
mesh_terms: D002117:Calcitriol / Q000494:pharmacology*; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D016207:Cytokines / Q000494:pharmacology; D004804:Eosinophils / Q000187:drug effects / Q000502:physiology; D006801:Humans; D019718:Receptors, CXCR4 / Q000276:immunology*; D015854:Up-Regulation; D014815:Vitamins / Q000494:pharmacology*
chemical_list: C527276:CXCR4 protein, human; D016207:Cytokines; D019718:Receptors, CXCR4; D014815:Vitamins; D002117:Calcitriol