M2a macrophage can rescue proliferation and gene expression of benign prostate hyperplasia epithelial and stroma cells from insulin‐like growth factor 1 knockdown

Abstract

Background Benign prostatic hyperplasia (BPH) is a common disease in elderly men and is often accompanied by chronic inflammation. Macrophages (several subtypes) are the main inflammatory cells that infiltrate the hyperplastic prostate and are found to secrete cytokines and growth factors. The current study aims to explore the effect of M2a macrophages on the development of BPH via insulin‐like growth factor 1 (IGF‐1). Methods Human prostate tissues, prostate, and monocyte cell lines (WPMY‐1, BPH‐1, and THP‐1) were used. THP‐1 was polarized into several subtypes with cytokines. The expression and localization of IGF‐1 and M2 macrophages were determined via immunofluorescent staining, quantitative real‐time polymerase chain reaction, and Western blot analysis. Flow cytometry and 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyl tetrazolium bromide (MTT) assays were used to investigate the effects of different subtypes of macrophages on prostate cells. IGF‐1 in WPMY‐1 and BPH‐1 cells was silenced and cocultured with or without M2a macrophages. Cell proliferation, apoptosis, cell cycle, epithelial–mesenchymal transition (EMT), and fibrosis processes were examined. Results The polarized subtypes of macrophages were verified by amplifying their specific markers. M2a macrophages enhanced prostate cell proliferation more significantly and CD206 was more expressed in hyperplastic prostate. IGF‐1 was localized in both epithelial and stromal components of prostate and upregulated in BPH tissues. M2a macrophages expressed more IGF‐1 than other subtypes. Knockdown of IGF‐1 in WPMY‐1 and BPH‐1 cells attenuated cell proliferation, promoted cell apoptosis, retarded cell cycle at the G0/G1 phase, and suppressed the EMT process in BPH‐1 cells as well as the fibrotic process in WPMY‐1 cells, which was reversible when cocultured with M2a macrophages. Conclusion These data demonstrated that knockdown of IGF‐1 expression in cultured BPH epithelial and stromal cells reduces proliferation and increases apoptosis. These effects are reversed by coculture with M2a macrophages.

Immune Cell Proinflammatory Microenvironment and Androgen-Related Metabolic Regulation During Benign Prostatic Hyperplasia in Aging

“…The results showed that M2a macrophages expressed more IGF-1 than other subtypes ( 29 ) ( Figure 1 ). Knockdown of IGF-1 in WPMY-1 and BPH-1 cells attenuated cell proliferation, promoted cell apoptosis, retarded the cell cycle at the G0/G1 phase, and suppressed the EMT process in BPH-1 cells as well as the fibrotic process in WPMY-1 cells, which was reversible when cocultured with M2a macrophages ( 29 ). These data demonstrated that knockdown of IGF-1 expression in cultured BPH epithelial and stromal cells reduces proliferation and increases apoptosis.…”

“…These data demonstrated that knockdown of IGF-1 expression in cultured BPH epithelial and stromal cells reduces proliferation and increases apoptosis. These effects are reversed by coculture with M2a macrophages ( 29 ). This indicates the direction for the precise treatment of BPH in the future ( Figure 1 ).…”

“…They mainly secrete cytokines and growth factors to promote the disease process of benign prostatic hyperplasia ( 28 ). Recently, based on human prostate tissues, prostate, and monocyte cell lines (WPMY-1, BPH-1, and THP-1), researchers have examined prostate cell proliferation, apoptosis, the cell cycle, epithelial-mesenchymal transition (EMT) and the process of fibrosis to explore the influence of M2a macrophages in the disease process of BPH ( 29 ). The results showed that M2a macrophages expressed more IGF-1 than other subtypes ( 29 ) ( Figure 1 ).…”

Connecting the Dots Between the Gut–IGF-1–Prostate Axis: A Role of IGF-1 in Prostate Carcinogenesis

“…How IGF-1 signaling affects adrenal and testes function remains unknown ( 32 ). The role of IGF-1 signaling in prostate development and normal prostate physiology has not been established in vivo , however, silencing IGF-1 in not only the WPMY-1 prostate stroma cell line, and but also BPH-1, a prostate epithelium cell line, decreased cell proliferation and increased apoptosis rate in vitro ( 33 ). In human, IGF1R is located on the long arm of chromosome 15, and 36 different probable mutations have been reported ( 34 ).…”

“…However, the gene expression of IGF-1 in prostate tissue was significantly increased (P = 0.001) and the expression of IGFBP3 was significantly decreased (P = 0.003) in patients with larger prostate size (>30 mL) ( 43 ). Local IGF-1 was reportedly upregulated in hyperplastic prostate tissues ( 33 ). Patients with acromegaly characterized by GH hypersecretion display high IGF-1 levels, and acromegaly patients are highly susceptible to IGF-1 related diseases including diabetes mellitus and BPH, suggesting IGF-1 regulation of various diseases.…”