Chronic inflammation has a role in the pathogenesis of benign prostatic hyperplasia (BPH) and prostate cancer. Mast cells have been detected in chronic inflammatory infiltrate of the prostate, and it is possible that the interaction between prostate epithelial cells and Trichomonas vaginalis influences the activity of mast cells in the prostate stroma. Activated mast cells might influence the biological functions of nearby tissues and cells. In this study, we investigated whether mast cells reacted with the culture supernatant of BPH epithelial cells infected with T. vaginalis may induce the proliferation of prostate stromal cells.
To measure the proliferation of prostate stromal cells in response to chronic inflammation caused by the infection of BPH-1 cells with T. vaginalis, the CCK-8 assay and wound healing assay were used. ELISAs, quantitative real-time PCR, western blotting and immunofluorescence were used to measure the production and expression of inflammatory cytokine and cytokine receptor.
BPH-1 cells incubated with live trichomonads produced increased levels of CCL2, IL-1β, IL-6, and CXCL8, and induced the migration of mast cells and monocytes. When the culture supernatant of BPH-1 cells stimulated with trichomonads (TCM) was added to mast cells, they became activated, as confirmed by release of β-hexosaminidase and CXCL8. Prostate stromal cells incubated with the culture supernatant of mast cells activated with TCM (M-TCM) proliferated and expressed increased levels of CXCL8, CCL2, and the cytokine receptors CXCR1 and CCR2. Blocking the chemokine receptors reduced the proliferation of stromal cells and also decreased the production of CXCL8 and CCL2. Moreover, the expression of FGF2, cyclin D1, and Bcl-2 was increased in the proliferated stromal cells stimulated with M-TCM. Additionally, the M-TCM-treated stromal cells were more invasive than control cells.
The inflammatory mediators released by BPH epithelial cells in response to infection by trichomonads induce the migration and activation of mast cells. The activated mast cells induce the proliferation of prostate stromal cells via CXCL8-CXCR1 and CCL2-CCR2 signaling. Our results therefore show that the inflammatory response by BPH epithelial cells stimulated with T. vaginalis induce the proliferation of prostate stromal cells via crosstalk with mast cells. Prostate © 2016 Wiley Periodicals, Inc.
The Prostate. 2016 Jun 21 [Epub ahead of print]
Jung-Hyun Kim, Sang-Su Kim, Ik-Hwan Han, Seobo Sim, Myoung-Hee Ahn, Jae-Sook Ryu
Department of Environmental Biology and Medical Parasitology, Hanyang University College of Medicine, Seoul, Korea., Department of Environmental Biology and Medical Parasitology, Hanyang University College of Medicine, Seoul, Korea., Department of Environmental Biology and Medical Parasitology, Hanyang University College of Medicine, Seoul, Korea., Department of Environmental and Tropical Medicine, Research Institute of Medical Science, Konkuk University School of Medicine, Chungju, Korea., Department of Environmental Biology and Medical Parasitology, Hanyang University College of Medicine, Seoul, Korea., Department of Environmental Biology and Medical Parasitology, Hanyang University College of Medicine, Seoul, Korea.