Department of Urology, Zhangzhou Affiliated Hospital of Fujian Medical University, Zhangzhou, Fujian, 363000, PR China.
Department of Urology, Zhangzhou Affiliated Hospital of Fujian Medical University, Zhangzhou, Fujian, 363000, PR China.
Tissue Cell. 2020 Jun;64:101343. doi: 10.1016/j.tice.2020.101343. Epub 2020 Jan 23.
Considering the association of macrophage migration inhibitory factor with development of prostate diseases, this study aims to explore the effect and mechanism of macrophages (MAs) in inflammation and proliferation of benign prostate hyperplasia (BPH) cells.
Totally 85 prostate tissues (75 from BPH patients and 10 from brain death patients) were collected for determination of biomarkers of T lymphocyte (CD4 and CD8), B lymphocyte (CD20) and MAs (CD68), as well as androgen receptor (AR) and CD40/CD40L. MAs stimulated by phorbol myristate acetate (PMA) were cultured with BPH cells (BPH-1), followed by AR inhibitor or anti-CD40 L antibody treatment. Proliferation and cell apoptosis were observed by MTT assay, colony formation assay and flow cytometer. Expressions of apoptotic related proteins and MAPK signaling pathway-related proteins were determined by qRT-PCR and Western blot.
BPH tissues had increased expressions of AR, CD40 and CD40 L, as well as elevated expressions of inflammation biomarkers (CD4, CD8, CD20 and CD68) in comparison to normal prostate tissues. MAs could increase the expressions of lymphocytes and inflammation biomarkers, in addition to promoting cell proliferation and inhibiting cell apoptosis. Cell proliferation and inflammation reaction could be attenuated by anti-CD40 L antibody and AR inhibitor in a concentration dependent manner through inhibiting the phosphorylation of JNK, ERK1/2 and p38.
MAs regulate AR and CD40/CD40L expression to promote the inflammation and proliferation as well as inhibiting apoptosis of BPH-1 cells through activation of the MAPK signaling pathway. This conclusion may provide a therapeutic strategy for BPH patients.
鉴于巨噬细胞移动抑制因子与前列腺疾病发展的关联，本研究旨在探讨巨噬细胞（MAs）在良性前列腺增生（BPH）细胞炎症和增殖中的作用及机制。
共收集 85 例前列腺组织（75 例来自 BPH 患者，10 例来自脑死亡患者），用于测定 T 淋巴细胞（CD4 和 CD8）、B 淋巴细胞（CD20）和 MAs（CD68）以及雄激素受体（AR）和 CD40/CD40L 的生物标志物。用佛波醇肉豆蔻酸酯（PMA）刺激 MAs 与 BPH 细胞（BPH-1）共培养，然后用 AR 抑制剂或抗 CD40L 抗体处理。通过 MTT 检测、集落形成检测和流式细胞术观察增殖和细胞凋亡。通过 qRT-PCR 和 Western blot 测定凋亡相关蛋白和 MAPK 信号通路相关蛋白的表达。
与正常前列腺组织相比，BPH 组织中 AR、CD40 和 CD40L 的表达增加，炎症生物标志物（CD4、CD8、CD20 和 CD68）的表达也升高。MAs 可增加淋巴细胞和炎症生物标志物的表达，促进细胞增殖，抑制细胞凋亡。抗 CD40L 抗体和 AR 抑制剂可通过抑制 JNK、ERK1/2 和 p38 的磷酸化，浓度依赖性地减弱细胞增殖和炎症反应。
MAs 通过激活 MAPK 信号通路调节 AR 和 CD40/CD40L 的表达，促进 BPH-1 细胞的炎症和增殖，抑制凋亡。这一结论可能为 BPH 患者提供一种治疗策略。
