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Trichomonas vaginalis (Tv), a protozoan parasite causing sexually-transmitted disease, has been detected in tissue of prostatitis, benign prostatic hyperplasia (BPH) and prostate cancer (PCa). IL-6, a mediator of chronic inflammation, induces the progression of prostate cancer, and influences the polarization of M2 macrophages, which are the main tumor-associated macrophages. We investigated whether IL-6 produced by human prostate epithelial cells stimulated with Tv induces the M2 polarization of THP-1-derived macrophages, which in turn promotes the progression of PCa. Conditioned medium was prepared from Tv-infected (TCM) and uninfected (CM) prostate epithelial cells (RWPE-1). Thereafter conditioned medium was prepared from macrophages after incubation with CM (M-CM) or TCM (M-TCM). RWPE-1 cells infected with Tv produced IL-6 and chemokines such as CCL2 and CXCL8. When human macrophages were treated with conditioned medium of RWPE-1 cells co-cultured with Tv (TCM), they became polarized to M2-like macrophages as indicated by the production of IL-10 and TGF-β, and the expression of CD36 and arginase-1, which are M2 macrophage markers. Moreover, proliferation of the M2-like macrophages was also increased by TCM. Blockade of IL-6 signaling with IL-6 receptor antibody and JAK inhibitor (Ruxolitinib) inhibited M2 polarization of THP-1-derived macrophages and proliferation of the macrophages. To assess the effect of crosstalk between macrophages and prostate epithelial cells inflamed by Tv infection on the growth of prostate cancer (PCa) cells, PC3, DU145 and LNCaP cells were treated with conditioned medium from THP-1-derived macrophages stimulated with TCM (M-TCM). Proliferation and migration of the PCa cells were significantly increased by the M-TCM. Our findings suggest that IL-6 produced in response to Tv infection of the prostate has an important effect on the tumor microenvironment by promoting progression of PCa cells following induction of M2 macrophage polarization. Author summary: In male, T. vaginalis infection have been proposed to involve in several prostate diseases such as prostatitis, benign prostatic hyperplasia and prostate cancer. However, studies for these mechanisms have been rare. We have previously reported that T. vaginalis induce the production of inflammatory cytokines in prostate cells. Among these cytokines, IL-6 have been reported to play an important role in M2 macrophage polarization, which lead to formation of tumor microenvironment in various cancers. Here we show that IL-6 produced by T. vaginalis infection in prostate epithelial cells induces M2 polarization of macrophages and these macrophages promote proliferation of prostate cancer cells. These findings suggest that T. vaginalis indirectly induces progression of prostate cancer by creating a tumor microenvironment through an inflammatory response. [ABSTRACT FROM AUTHOR]

Trichomoniasis, which is caused by Trichomonas vaginalis, is one of the most common non-viral sexually transmitted infections; however, limited population-based data are available that describe patterns and trends of the disease. We summarized insurance claims of trichomoniasis cases reported during 2009–2014 to South Korea Health Insurance Review and Assessment Service. The average annual incidence in South Korea was 276.8 persons per 100,000 population, and a substantial sex-associated variation was observed. The incidence rate among female subjects trended upward over 6 years, that is, it increased from 501 in 2009 to 625.8 in 2014 per 100,000 female population, which indicates a 25% overall increase. This trend was sharpest in the ≥60 years group of female population. However, a 66% decrease in incidence rates was observed among male subjects (23.7 in 2009 to 15.7 in 2014 per 100,000 male population). Further, substantial decrease was observed in the ≥40 years groups of male population. The incidence of trichomoniasis varied across regions and was the highest in Jeju province of South Korea. Overall, as the incidence of trichomoniasis appears to have increased in South Korea during 2009–2014, the disease burden is increasing; hence, there is a need to better understand the disease transmission. [ABSTRACT FROM AUTHOR]

To elucidate the roles of metalloproteinases and the Bcl-2 family of proteins in Trichovaginalis. vaginalis-induced apoptosis in human cervical cancer cells (SiHa cells) and vaginal epithelial cells (MS74 cells), SiHa cells and MS74 cells were incubated with live T. vaginalis, T. vaginalis excretory and secretory products (ESP), and T. vaginalis lysates, either with or without the specific metalloproteinase inhibitor 1,10-phenanthroline (1,10-PT), and examined apoptotic events and Bcl-2 signaling. The live T. vaginalis and the T. vaginalis ESP induced the release of cytochrome c into the cytosol, the activation of caspase-3 and caspase-9, and the cleavage of PARP. Additionally, the live T. vaginalis, but not the T. vaginalis lysate, induced the cleavage of the proapoptotic Bim protein. The live T. vaginalis and the T. vaginalis ESP, but not the T. vaginalis lysate, induced the dose-dependent cleavage of the antiapoptotic Bcl-xL and Mcl-1 proteins and decreased the association levels of Bcl-xL/Bim and Mcl-1/Bim complexes. We performed gelatin zymography and casein-hydrolysis assays on the live T. vaginalis and the T. vaginalis ESP to identify the apoptosis-inducing factor. Both the live T. vaginalis and the ESP contained high levels of metalloproteinases, of which activities were significantly inhibited by 1,10-PT treatment. Furthermore, the 1,10-PT blocked the cleavage of Bcl-xL, Mcl-1, PARP, caspase-3, and caspase-9, as well as the release of cytochrome c into the cytosol, and it significantly increased the association levels of the Bcl-xL/Bim and Mcl-1/Bim protein complexes, returning them to normal levels. Our results demonstrate that T. vaginalis induces mitochondria-dependent apoptosis in SiHa cells through the dissociation of Bcl-xL/Bim and Mcl-1/Bim complexes and that the apoptosis is blocked by the metalloproteinase inhibitor 1,10-PT. These results expand our understanding of the role of metalloproteinases in T. vaginalis-induced apoptosis and the signaling pathway in trichomoniasis of the cervicovaginal epithelial cells. [ABSTRACT FROM AUTHOR]