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. AIM: 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. MATERIALS AND 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. PMID: 20386089 [PubMed - indexed for MEDLINE]

Human prostatic urethra expresses Vitamin D receptor and responds to Vitamin D receptor ligation / P. Comeglio; A.K. Chavalmane; B. Fibbi; S. Filippi; M. Marchetta; M. Marini; A. Morelli; G. Penna; L. Vignozzi; G.B. Vannelli; L. Adorini; M. Maggi.. - In: JOURNAL OF ENDOCRINOLOGICAL INVESTIGATION. - ISSN 0391-4097. - STAMPA. - 33:(2010), pp. 730-738. [10.3275/6974]

Human prostatic urethra expresses Vitamin D receptor and responds to Vitamin D receptor ligation.

COMEGLIO, PAOLO;FIBBI, BENEDETTA;FILIPPI, SANDRA;MARINI, MIRCA;MORELLI, ANNAMARIA;VIGNOZZI, LINDA;VANNELLI, GABRIELLA;MAGGI, MARIO
2010

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. AIM: 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. MATERIALS AND 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. PMID: 20386089 [PubMed - indexed for MEDLINE]
2010
33
730
738
Goal 3: Good health and well-being for people
P. Comeglio; A.K. Chavalmane; B. Fibbi; S. Filippi; M. Marchetta; M. Marini; A. Morelli; G. Penna; L. Vignozzi; G.B. Vannelli; L. Adorini; M. Maggi.
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Utilizza questo identificatore per citare o creare un link a questa risorsa: https://hdl.handle.net/2158/386912
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