Leptin is a type of adipokine mainly produced by adipocytes and reported to be overproduced in prostate cancer. However, it is not known whether it stimulates the proliferation of prostate cells. In this study, we investigated whether benign prostatic hyperplasia epithelial cells (BPH-1 cells) infected with Trichomonas vaginalis induced the proliferation of prostate cells via a leptin signaling pathway. To investigate the effect of crosstalk between adipocyte leptin and inflamed epithelial cell in proliferation of prostate cells, adipocytes 3T3-L1 cells were incubated in conditioned medium of BPH-1 cells infected with T. vaginalis (T. vaginalis-conditioned medium, TCM), and then the adipocyte-conditioned medium (ATCM) was identified to cause proliferation of prostate cells. BPH-1 cells incubated with live T. vaginalis released pro-inflammatory cytokines, and conditioned medium of these cells caused migration of adipocytes. When prostate stromal cells and BPH-1 cells were incubated with adipocyte conditioned medium containing leptin, their growth rates increased as did expression of the leptin receptor (known as OBR) and signaling molecules such as JAK2/STAT3, Notch and survivin. Moreover, blocking the OBR reduced this proliferation and the expression of leptin signaling molecules in response to ATCM. In conclusion, our findings show that inflamed BPH-1 cells infected with T. vaginalis induce the proliferation of prostate cells through leptin-OBR signaling. Therefore, it is likely that T. vaginalis contributes to prostate enlargement in BPH via adipocyte leptin released as a result of inflammation of the prostate.

Trichomonas vaginalis (Tv), a protozoan parasite causing sexually transmitted disease, has been detected in the tissue of prostatitis, benign prostatic hyperplasia (BPH) and prostate cancer and vaginal discharge in vaginitis. [1][2][3] Mast cells are known to be associated with Tv infection; it is observed in the vaginal wall or vaginal smear of a woman infected with Tv, 4 and it is increased in the tissues of rat prostatitis experimentally infected with Tv. 5 The inflammatory mediator of Tv-infected vaginal epithelial cells or benign prostatic hyperplasia epithelial cells induces chemotaxis of mast cells. 6,7 However, there are few reports that these mast cells are involved in prostate cells proliferation.Mast cells are known to be important effector cells in tissue fibrosis. Mast cell activation and degranulation lead to the release of inflammatory and profibrotic mediators that promote tissue fibrosis. 8 Tryptase is the most abundant secretory granule-derived serine proteinase in mast cells and has been reported to induce human lung fibroblast migration, myoblast proliferation and cardiac fibroblast activation via protease-activated receptor 2 (PAR2). [9][10][11]