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

Abstract INTRODUCTION AND OBJECTIVES 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. METHODS 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‐β1, 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. RESULTS 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. CONCLUSIONS 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. Prostate 56: 171–182, 2003. © 2003 Wiley‐Liss, Inc.