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.

中文翻译：

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阴道毛滴虫刺激的前列腺上皮细胞产生的IL-6通过诱导THP-1衍生的巨噬细胞的M2极化来促进前列腺癌细胞的增殖。

阴道毛滴虫（Tv）是一种引起性传播疾病的原生动物寄生虫，已在前列腺炎，良性前列腺增生（BPH）和前列腺癌（PCa）组织中检测到。IL-6是慢性炎症的介质，可诱导前列腺癌的进展，并影响M2巨噬细胞的极化，M2巨噬细胞是与肿瘤相关的主要巨噬细胞。我们研究了由Tv刺激的人前列腺上皮细胞产生的IL-6是否诱导THP-1衍生的巨噬细胞的M2极化，进而促进PCa的进程。从Tv感染（TCM）和未感染（CM）前列腺上皮细胞（RWPE-1）中制备条件培养基。此后，在与CM（M-CM）或TCM（M-TCM）孵育后，从巨噬细胞制备条件培养基。被电视感染的RWPE-1细胞产生IL-6和趋化因子，例如CCL2和CXCL8。当将人巨噬细胞用与Tv（TCM）共培养的RWPE-1细胞的条件培养基处理时，它们被极化为M2样巨噬细胞，如IL-10和TGF-β的产生以及CD36和CD精氨酸酶-1，它们是M2巨噬细胞标记。而且，中药也增加了M2样巨噬细胞的增殖。用IL-6受体抗体和JAK抑制剂（Ruxolitinib）阻断IL-6信号传导可抑制THP-1衍生的巨噬细胞的M2极化和巨噬细胞的增殖。为了评估巨噬细胞和电视感染发炎的前列腺上皮细胞之间的串扰对前列腺癌细胞（PCa）PC3生长的影响，DU145和LNCaP细胞用TCM-1（M-TCM）刺激的THP-1衍生巨噬细胞的条件培养基处理。M-TCM显着增加了PCa细胞的增殖和迁移。我们的发现表明响应前列腺电视感染而产生的IL-6通过促进M2巨噬细胞极化后促进PCa细胞的进程，对肿瘤微环境具有重要影响。