Impact of immune inflammation on the proliferation and apoptosis of benign prostatic hyperplasia cells.
- Author:
Ming-Gen YANG
1
;
Zhen-Qiang XU
1
Author Information
1. Department of Urology, Zhangzhou Hospital Affiliated to Fujian Medical University, Zhangzhou, Fujian 363000, China.
- Publication Type:Journal Article
- Keywords:
CD40/CD40L pathway;
androgen receptor pathway;
benign prostate hyperplasia;
immune inflammation;
proliferation
- MeSH:
Apoptosis;
Cell Proliferation;
Humans;
Inflammation;
Prostatic Hyperplasia
- From:
National Journal of Andrology
2021;27(10):867-875
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the impact of macrophage-induced immune inflammation on the proliferation and apoptosis of BPH cells and its possible mechanism.
METHODS:Macrophages were stimulated with phorbol myristate acetate, co-cultured with BPH-1 cells, and then treated with the androgen receptor (AR) inhibitor or anti-CD40L antibody. The immunohistochemical biomarkers of the T lymphocytes (CD4 and CD8), B lymphocyte (CD20) and macrophages (CD68), AR, CD40/CD40L, and inflammatory factors IL-1, IL-6 and TNF-α were measured before and after treatment. The proliferation and apoptosis of the cells were observed by MTT assay, colony-forming assay and flow cytometry, and the expressions of cell apoptosis- and MAPK signaling pathway-related proteins were determined by qRT-PCR and Western blot.
RESULTS:Significantly increased proliferation and decreased apoptosis of the cells, up-regulated expressions of Bcl-2, IL-1, IL-6, TNF-α, AR, CD40 and CD40L, and down-regulated expression of Bax were observed in the BPH-1 cells co-cultured with macrophages (the M-BPH-1 group) compared with those in the blank control (B-BPH-1) group (P < 0.01). In comparison with the BPH-1 cells treated with normal saline, those treated with either low-dose CD40L (L-CD40L) or high-dose CD40L (H-CD40L) showed markedly inhibited proliferation, increased apoptosis, up-regulated expression of Bax, and down-regulated expressions of Bcl-2, IL-1, IL-6 and TNF-α (P < 0.01), and those in the low- and high-dose AR (L-AR and H-AR) inhibitor groups exhibited remarkably reduced proliferation, increased apoptosis, down-regulated expressions of Bcl-2, IL-1, IL-6 and TNF-α, and up-regulated expression of Bax (P < 0.01). The phosphorylation levels of JNK, ERK and P38 were significantly elevated in the M-BPH-1 group, but declined in the H-CD40L and the H-AR inhibitor groups compared with those in the B-BPH-1 group, all in a concentration-dependent manner (P < 0.01).
CONCLUSIONS:Macrophage-induced immune inflammation regulates AR and CD40/CD40L expressions and promotes the proliferation and inhibits the apoptosis of BPH-1 cells by activating the MAPK signaling pathway. /.
