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Abstract

Volume 24, Issue 5 (September 2022) 24, 513–520; 10.4103/aja2021114

Combined treatment with dihydrotestosterone and lipopolysaccharide modulates prostate homeostasis by upregulating TNF-α from M1 macrophages and promotes proliferation of prostate stromal cells

Yu Tong1, Yi-Jun Guo1, Qin Zhang2, Hai-Xia Bi2, Kai Kai1, Ren-Yuan Zhou1

1 Department of Urology, Jing'an District Central Hospital, Fudan University, Shanghai 200040, China
2 Department of Pathology, Jing'an District Central Hospital, Fudan University, Shanghai 200040, China

Correspondence: Dr. RY Zhou (zhourenyuan@189.cn)

Date of Submission 28-Jul-2021 Date of Acceptance 23-Nov-2021 Date of Web Publication 31-Dec-2021

Abstract

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.

Keywords: benign prostatic hyperplasia; dihydrotestosterone; inflammation; macrophage; tumor necrosis factor-alpha

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