Sexual Medicine and Andrology Unit, Department of Clinical Physiopathology, University of Florence, Viale Pieraccini 6, Florence 50139, Italy.
J Endocrinol. 2012 Jul;214(1):31-43. doi: 10.1530/JOE-12-0142. Epub 2012 May 4.
Progression of benign prostatic hyperplasia (BPH) involves chronic inflammation and immune dysregulation. Preclinical studies have demonstrated that prostate inflammation and tissue remodeling are exacerbated by hypogonadism and prevented by testosterone 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 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 testosterone level was performed. Even after adjusting for confounding factors, hypogonadism was associated with a fivefold increased risk of intraprostatic inflammation, which was also more severe than that observed in eugonadal BPH patients. Triggering hBPH cells by inflammatory stimuli (tumor necrosis factor α, lipopolysaccharide, or CD4(+)T cells) induced abundant secretion of inflammatory/growth factors (interleukin 6 (IL6), IL8, and basic fibroblast growth factor (bFGF)). Co-culture of CD4(+)T cells with hBPH cells induced secretion of Th1 inducer (IL12), Th1-recruiting chemokine (interferon γ inducible protein 10, IP10), and Th2 (IL9)- and Th17 (IL17)-specific cytokines. Pretreatment with DHT inhibited NF-κB activation and suppressed secretion of several inflammatory/growth factors, with the most pronounced effects on IL8, IL6, and bFGF. Reduced inflammatory cytokine production by T-cells, an increase in IL10, and a significant reduction of T cells proliferation suggested that DHT exerted a broad anti inflammatory effect on testosterone cells [corrected]. 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.
良性前列腺增生症（BPH）的进展涉及慢性炎症和免疫失调。临床前研究表明，前列腺炎症和组织重塑会因性腺功能减退而加剧，并可通过睾酮补充来预防。我们现在研究了在人类中，性腺功能减退是否与更严重的 BPH 炎症有关，以及选择性雄激素受体激动剂二氢睾酮（DHT）对源自 BPH 患者的基质细胞（hBPH）培养物的体外作用。对 BPH 患者前列腺切除术标本中的炎症浸润进行组织学分析，并与血清睾酮水平进行相关性分析。即使在调整混杂因素后，性腺功能减退与前列腺内炎症的风险增加五倍相关，且比性腺功能正常的 BPH 患者观察到的炎症更为严重。炎性刺激（肿瘤坏死因子-α、脂多糖或 CD4+T 细胞）触发 hBPH 细胞，诱导大量炎症/生长因子（白细胞介素 6（IL6）、IL8 和碱性成纤维细胞生长因子（bFGF））的分泌。CD4+T 细胞与 hBPH 细胞共培养诱导 Th1 诱导剂（IL12）、Th1 募集趋化因子（干扰素γ诱导蛋白 10，IP10）和 Th2（IL9）和 Th17（IL17）特异性细胞因子的分泌。DHT 预处理抑制 NF-κB 激活并抑制几种炎症/生长因子的分泌，对 IL8、IL6 和 bFGF 的抑制作用最为明显。T 细胞产生的炎症细胞因子减少、IL10 增加以及 T 细胞增殖显著减少表明 DHT 对睾酮细胞发挥了广泛的抗炎作用[更正]。总之，我们的数据表明，DHT 对人前列腺基质细胞发挥免疫调节作用，抑制其主动诱导和/或维持自身免疫和炎症反应的潜力。
