Department of Urology, Jing'an District Central Hospital, Fudan University, Shanghai 200040, China.
Department of Pathology, Jing'an District Central Hospital, Fudan University, Shanghai 200040, China.
Asian J Androl. 2022 Sep-Oct;24(5):513-520. doi: 10.4103/aja2021114.
Androgens and chronic inflammation, which play essential roles in the development of benign prostatic hyperplasia (BPH), are considered to be important factors in disorders of prostate homeostasis. These two factors may lead to pathological hyperplasia in the prostate transition zone of patients with BPH. However, few studies have examined the mechanism of how dihydrotestosterone (DHT) affects chronic inflammation in prostate tissue during the progression of BPH. This study examined the performance of DHT in lipopolysaccharide-treated M1 macrophages and the subsequent effects on the proliferation of prostate stromal and epithelial cells. We found that DHT increased secretion of the pro-inflammatory factor tumor necrosis factor (TNF)-α from M1 macrophages differentiated from THP-1 cells. The supernatant of M1 macrophages promoted the proliferation of WPMY-1 prostate stromal cells by upregulating B-cell lymphoma-extra large (Bcl-xL) and cellular Myc (c-Myc) levels by activating TNF-α-mediated nuclear factor-kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) pathways. Moreover, this supernatant increased the expression of androgen receptor in WPMY-1 cells, which was TNF-α-independent. Additionally, TNF-α protein expression was significantly higher in patients with BPH and a large prostate volume than that in those with a small prostate volume. Further analysis showed that higher serum testosterone combined with prostate-specific androgen concentrations was related to TNF-α expression. This study suggests that DHT modulates the inflammatory environment of BPH by increasing TNF-α expression from lipopolysaccharide-treated M1 macrophages and promotes the proliferation of prostate stromal cells. Targeting TNF-α, but not DHT, may be a promising strategy for patients with BPH.
雄激素和慢性炎症在良性前列腺增生症（BPH）的发展中起着重要作用，被认为是前列腺动态平衡紊乱的重要因素。这两个因素可能导致 BPH 患者前列腺移行区发生病理性增生。然而，很少有研究探讨二氢睾酮（DHT）在 BPH 进展过程中如何影响前列腺组织的慢性炎症。本研究研究了 DHT 在脂多糖处理的 M1 巨噬细胞中的作用及其对前列腺基质和上皮细胞增殖的后续影响。我们发现 DHT 增加了从 THP-1 细胞分化的 M1 巨噬细胞中促炎因子肿瘤坏死因子（TNF）-α的分泌。M1 巨噬细胞的上清液通过激活 TNF-α 介导的核因子-κB（NF-κB）和丝裂原活化蛋白激酶（MAPK）通路，上调 B 细胞淋巴瘤-extra large（Bcl-xL）和细胞 Myc（c-Myc）水平，促进 WPMY-1 前列腺基质细胞的增殖。此外，该上清液增加了 WPMY-1 细胞中雄激素受体的表达，而这与 TNF-α无关。此外，与小前列腺体积的患者相比，BPH 患者和大前列腺体积患者的 TNF-α 蛋白表达明显更高。进一步分析表明，较高的血清睾酮结合前列腺特异性雄激素浓度与 TNF-α 表达有关。本研究表明，DHT 通过增加脂多糖处理的 M1 巨噬细胞中 TNF-α 的表达来调节 BPH 的炎症环境，并促进前列腺基质细胞的增殖。靶向 TNF-α，而不是 DHT，可能是 BPH 患者的一种有前途的治疗策略。
