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

Prostate. 2003 Aug 1;56(3):171-82. doi: 10.1002/pros.10238.

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-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.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Carcinoma / genetics*
  • Carcinoma / physiopathology*
  • Enzyme-Linked Immunosorbent Assay
  • Gene Expression Regulation, Neoplastic*
  • Homeostasis
  • Humans
  • Immunohistochemistry
  • Inflammation
  • Interleukin-17 / biosynthesis*
  • Interleukin-17 / pharmacology*
  • Interleukin-6 / biosynthesis
  • Interleukin-8 / biosynthesis
  • Male
  • Polymerase Chain Reaction
  • Prostatic Hyperplasia / genetics*
  • Prostatic Hyperplasia / physiopathology*
  • Prostatic Neoplasms / genetics*
  • Prostatic Neoplasms / physiopathology*
  • RNA, Messenger / analysis
  • Receptors, Interleukin / biosynthesis*
  • Receptors, Interleukin-17
  • Recombinant Proteins / biosynthesis*
  • Recombinant Proteins / pharmacology*
  • Up-Regulation

Substances

  • IL17RA protein, human
  • Interleukin-17
  • Interleukin-6
  • Interleukin-8
  • RNA, Messenger
  • Receptors, Interleukin
  • Receptors, Interleukin-17
  • Recombinant Proteins