Interleukin-17 Induces Expression of Chemokines and Cytokines in Prostatic Epithelial Cells but Does Not Stimulate Cell Growth In Vitro.

Background: Interleukin-17 (IL-17A) expression is increased in prostate cancer. This study investigated the expression of IL-17A receptor C (IL-17RC) in prostatic intraepithelial neoplasia (PIN) lesions and the effects of IL-17A on prostatic epithelial cells in studies.

Methods: IL-17RC expression in human and rodent prostate tissues was detected by immunohistochemistry. Quantitative real-time reverse-transcription polymerase chain reaction (qRT-PCR) and Western blot analyses were used to determine mRNA and protein expression in human and mouse prostatic epithelial cell lines.

Results: IL-17RC protein was increased in human and rodent PIN lesions, compared to the normal human and rodent prostatic epithelium. IL-17A treatment activated the Nuclear Factor-κB (NF-κB) and/or Extracellular signal-Regulated Kinase (ERK) pathways in human PIN and LNCaP cell lines as well as mouse prostate cancer cell line TRAMP-C1. IL-17A treatment did not affect cell growth of the cell lines studied. However, IL-17A induced expression of CXCL1, CXCL2, CCL2, CCL5, and IL-6 in human and mouse prostatic epithelial cell lines. When the full-length IL-17RC was over-expressed in human PIN and LNCaP cell lines, activation of NF-κB and/or ERK pathways and expression of CXCL1, CXCL2, and CCL5 chemokines were significantly enhanced upon IL-17A treatment.

Conclusion: These findings suggest that the prostatic epithelial cells in PIN lesions may respond to IL-17A stimuli with augmented synthesis of chemokines, due to increased IL-17RC expression.