Expression and function of pro-inflammatory interleukin IL-17 and IL-17 receptor in normal, benign hyperplastic, and malignant prostate.

Abstract

To investigate factors involved in inflammation of the prostate besides IL-15, we screened prostatic cells and tissues for IL-17 and IL-17 receptor expression. Normal prostate (n = 1), BPH (n = 19), and carcinoma (CaP, n = 12) specimens were screened for IL-17, IL-17 receptor, CD45, IL-6, and IL-8 mRNA expression. The carcinoma cell lines DU145, PC3, LNCaP, and BPH-epithelial (EC), stromal cell (SC) preparations, and BPH-T-cell lines were analyzed for IL-17 production by RT-PCR and ELISA. The effect of IL-17 on IL-6, IL-8, TGF-beta1, and fibroblast growth factor (FGF-2) mRNA expression and/or release of SC was analyzed using real-time PCR and/or ELISA. Immunohistochemistry was used to localize both IL-17 and IL-17 receptor. In the normal prostate, IL-17 expression was very weak and restricted to lymphocytes. In 79% of BPH and 58% of CaP specimens, IL-17 mRNA and protein expression was increased. IL-17 mRNA expression could be shown for activated BPH-T-cells and to some extend for BPH-EC. Expression of IL-17 receptor was ubiquitous. Release of IL-17 was shown only for activated BPH-T-cells. IL-17 stimulated expression of IL-6 (13-fold) and IL-8 (26-fold) by prostatic BPH-SC. In situ, however, the amount of IL-17mRNA in BPH-tissue did not correlate with the amount of IL-6 and IL-8 mRNA. In CaP tissue, significant correlation was found only between the amount of IL-6 and IL-8 mRNA. Activated BPH-T-cells abundantly express IL-17. The increase of IL-17 in BPH-tissues goes hand in hand with elevated levels of IL-15, a pro-inflammatory cytokine with T-cell growth factor properties. A clinical relevance of increased IL-17 expression under pathological conditions is suggested by the demonstration of significant upregulation of IL-6 and IL-8 production of prostatic SC by IL-17.