title: Human prostatic urethra expresses vitamin D receptor and responds to vitamin D receptor ligation.
abstract: BACKGROUND
  Chronic inflammation is now considered a determinant of benign prostatic hyperplasia (BPH), promoting, together with the hormonal milieu, prostate overgrowth and lower urinary tract symptoms (LUTS). Prostatic urethra actively participates in determining progression of LUTS associated with BPH.
  
  
  OBJECTIVE
  To investigate the expression of the vitamin D receptor (VDR) and the ability of the VDR agonist elocalcitol to reduce inflammatory responses in human prostatic urethra (hPU) cells.
  
  
  METHODS
  Human prostatic urethra, prostate and bladder neck were obtained from patients affected by BPH. Immunohistochemical studies for VDR expression were performed in tissue samples, from which primary cell cultures were also derived. In hPU cells, proliferation and chemiotaxis were studied, along with Rho kinase (ROCK) activity (MYPT-1 phosphorylation) by western blot. Quantitative RT-PCR was performed for VDR, cyclooxygenase (COX-2), and interleukin (IL)-8 expression.
  
  
  RESULTS
  Urethra displays higher VDR expression compared to prostate and bladder neck tissues. The VDR agonist elocalcitol partially reverts COX-2 and IL-8 mRNA upregulation induced by a pro-inflammatory cytokine mixture (IL-17, interferon-γ, tumor necrosis factor-α) and inhibits cell migration in urethral cells. Elocalcitol prevents activation of ROCK, as previously demonstrated in bladder and prostate cell cultures.
  
  
  CONCLUSIONS
  Our results suggest that prostatic urethra is, within the lower urinary tract, a novel target for VDR agonists, as shown by the capacity of elocalcitol to inhibit ROCK activity and to limit inflammatory responses in human primary urethra cells.
authors.affiliation: Andrology Unit, Department of Clinical Physiopathology, University of Florence, V.le Pieraccini 6, 50139 Florence, Italy.
authors.forename: P
authors.initials: P
authors.lastname: Comeglio
authors.forename: A K
authors.initials: AK
authors.lastname: Chavalmane
authors.forename: B
authors.initials: B
authors.lastname: Fibbi
authors.forename: S
authors.initials: S
authors.lastname: Filippi
authors.forename: M
authors.initials: M
authors.lastname: Marchetta
authors.forename: M
authors.initials: M
authors.lastname: Marini
authors.forename: A
authors.initials: A
authors.lastname: Morelli
authors.forename: G
authors.initials: G
authors.lastname: Penna
authors.forename: L
authors.initials: L
authors.lastname: Vignozzi
authors.forename: G B
authors.initials: GB
authors.lastname: Vannelli
authors.forename: L
authors.initials: L
authors.lastname: Adorini
authors.forename: M
authors.initials: M
authors.lastname: Maggi
mesh_terms: D000368:Aged; D002117:Calcitriol / Q000031:analogs & derivatives* / Q000494:pharmacology; D018929:Cell Culture Techniques; D002478:Cells, Cultured; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004353:Drug Evaluation, Preclinical; D015870:Gene Expression; D006801:Humans; D008024:Ligands; D008297:Male; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D011467:Prostate / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D011470:Prostatic Hyperplasia / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D018167:Receptors, Calcitriol / Q000819:agonists* / Q000235:genetics* / Q000378:metabolism; D014521:Urethra / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D001743:Urinary Bladder / Q000378:metabolism / Q000473:pathology
chemical_list: C487049:BXL628; D016207:Cytokines; D008024:Ligands; D018167:Receptors, Calcitriol; D002117:Calcitriol
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