Progression of benign prostatic hyperplasia (BPH) also involves chronic inflammation and immune dysregulation. Preclinical studies have demonstrated that prostate inflammation and tissue remodeling are exacerbated by hypogonadism and prevented by testosterone (T) supplementation. We now investigated whether, in humans, hypogonadism was associated with more severe BPH inflammation and the in vitro effect of the selective androgen receptor (AR) agonist dihydrotestosterone (DHT) on cultures of stromal cells derived from BPH patients (hBPH). Histological analysis of inflammatory infiltrates in prostatectomy specimens from a cohort of BPH patients, and correlation with serum T level was performed. Even after adjusting for confounding factors, hypogonadism was associated with a 5-fold increased risk of intraprostatic inflammation which resulted also more severe compared to that observed in eugonadal BPH-patients. Triggering hBPH cells by inflammatory stimuli (TNFα, LPS or CD4+ T cells) induced abundant secretion of inflammatory/growth factors (IL-8, IL-6, bFGF). Co-colture of CD4+ T cells with hBPH cells induced secretion of Th1-inducer (IL-12), Th1-recruiting chemokine (IP-10) and Th2- (IL-9) and Th17- (IL-17) specific cytokines. Pretreatment with DHT inhibited NF-κB activation and suppressed secretion of several inflammatory/growth factors-with the most pronounced effects on IL-8, IL-6 and bFGF. Reduced inflammatory cytokines production by T cells, an increase in IL-10 and a significant reduction of T cells proliferation suggested that DHT exerted a broad anti inflammatory effect on T cells. In conclusion, our data demonstrate that DHT exerts an immune regulatory role on human prostatic stromal cells, inhibiting their potential to actively induce and/or sustain autoimmune and inflammatory responses.

Anti-inflammatory effect of androgen receptor activation in human benign prostatic hyperplasia cells / Vignozzi L; Cellai I; Santi R; Lombardelli L; Morelli A; Comeglio P; Filippi S; Logiodice F; Carini M; Nesi G; Gacci M; Piccinni MP; Adorini L; Maggi M.. - In: JOURNAL OF ENDOCRINOLOGY. - ISSN 0022-0795. - STAMPA. - 214:(2012), pp. 31-43. [10.1530/JOE-12-0142]

Anti-inflammatory effect of androgen receptor activation in human benign prostatic hyperplasia cells.

VIGNOZZI, LINDA;CELLAI, ILARIA;SANTI, RAFFAELLA;LOMBARDELLI, LETIZIA;MORELLI, ANNAMARIA;COMEGLIO, PAOLO;FILIPPI, SANDRA;LOGIODICE, FEDERICA;CARINI, MARCO;NESI, GABRIELLA;GACCI, MAURO;PICCINNI, MARIE-PIERRE;MAGGI, MARIO
2012

Abstract

Progression of benign prostatic hyperplasia (BPH) also involves chronic inflammation and immune dysregulation. Preclinical studies have demonstrated that prostate inflammation and tissue remodeling are exacerbated by hypogonadism and prevented by testosterone (T) supplementation. We now investigated whether, in humans, hypogonadism was associated with more severe BPH inflammation and the in vitro effect of the selective androgen receptor (AR) agonist dihydrotestosterone (DHT) on cultures of stromal cells derived from BPH patients (hBPH). Histological analysis of inflammatory infiltrates in prostatectomy specimens from a cohort of BPH patients, and correlation with serum T level was performed. Even after adjusting for confounding factors, hypogonadism was associated with a 5-fold increased risk of intraprostatic inflammation which resulted also more severe compared to that observed in eugonadal BPH-patients. Triggering hBPH cells by inflammatory stimuli (TNFα, LPS or CD4+ T cells) induced abundant secretion of inflammatory/growth factors (IL-8, IL-6, bFGF). Co-colture of CD4+ T cells with hBPH cells induced secretion of Th1-inducer (IL-12), Th1-recruiting chemokine (IP-10) and Th2- (IL-9) and Th17- (IL-17) specific cytokines. Pretreatment with DHT inhibited NF-κB activation and suppressed secretion of several inflammatory/growth factors-with the most pronounced effects on IL-8, IL-6 and bFGF. Reduced inflammatory cytokines production by T cells, an increase in IL-10 and a significant reduction of T cells proliferation suggested that DHT exerted a broad anti inflammatory effect on T cells. In conclusion, our data demonstrate that DHT exerts an immune regulatory role on human prostatic stromal cells, inhibiting their potential to actively induce and/or sustain autoimmune and inflammatory responses.
2012
214
31
43
Vignozzi L; Cellai I; Santi R; Lombardelli L; Morelli A; Comeglio P; Filippi S; Logiodice F; Carini M; Nesi G; Gacci M; Piccinni MP; Adorini L; Maggi M.
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Utilizza questo identificatore per citare o creare un link a questa risorsa: https://hdl.handle.net/2158/629087
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