Chlamydia trachomatis infection increases the expression of inflammatory tumorigenic cytokines and chemokines as well as components of the Toll-like receptor and NF-κB pathways in human prostate epithelial cells

Inflammation has been reported to play a major role in prostate carcinogenesis. Several bacterial infections can lead to prostate inflammation; however, until now, the precise molecular and cellular mechanisms linking inflammation to carcinogenesis have remained unclear. We therefore investigated the initiation of inflammation induced by Chlamydia trachomatis (C. trachomatis) infection in human prostate epithelial cells using an in vitro culture system in which human androgen-independent PC-3 prostate cancer epithelial cells were infected with C. trachomatis serovar L2. The expression levels of VEGF, ICAM-1, IL-6, IL-8, IL-1β, TNFα, CCL5, CCL2 and iNOS inflammation-related genes, as well as genes involved in the Toll-like receptor (TLR) pathway (TLR2, TLR4, CD14 and MyD88), were evaluated at the mRNA level in infected PC-3 cells 24 h after infection with C. trachomatis serovar L2. The expression levels of components of the NF-κB pathway (p65 and IκBα) were evaluated at the mRNA level in infected PC-3 cells at different time points (1, 6, 12 and 24 h) after infection. The expression levels of inflammation-related genes, components of the Toll-like receptor pathway and genes involved in NF-κB activation were analyzed in infected and uninfected cells using semi-quantitative RT-PCR. We detected a significant increase (p < 0.001) in inflammation-related cytokines in infected PC-3 cells. During infection, PC-3 cells elicited a proinflammatory response, as shown by NF-κB activation, TLR2 and TLR4 upregulation and the increased expression of inflammation-related genes. Furthermore, we observed significant upregulation of the adhesion molecules ICAM-1 and VEGF, which are two biomarkers correlated with tumor progression and immune system evasion. The present study suggests that human prostate cancer epithelial cells are susceptible to C. trachomatis infection and upregulate proinflammatory markers during infection.