Increased expression of lymphocyte-derived cytokines in benign hyperplastic prostate tissue, identification of the producing cell types, and effect of differentially expressed cytokines on stromal cell proliferation

Prostate. 2002 Jun 1;52(1):43-58. doi: 10.1002/pros.10084.

Abstract

Background: Benign prostatic hyperplasia (BPH) frequently exhibit infiltration of CD4 (+)/CD45RO (+) memory-T-lymphocytes. Expression and impact of lymphocyte-derived growth factors on prostatic stromal cell (PSC) growth were investigated. METHODS; Lymphokine synthesis in normal prostate tissues (n = 3), BPH-tissues (n = 13), BPH-derived T-cells (n = 6), BPH-derived epithelial cells (BPH-EC) (n = 5), normal prostate-derived (n = 3) and BPH-derived stromal cell lines (BPH-SC) (n = 6), and prostate cancer (CaP) lines (n = 3) was analyzed by RT-PCR and Southern-blotting. The effect of interleukin (IL)-2, -4, -7, and interferon-gamma (IFN-gamma) on normal and BPH-SC growth was investigated by (3)H-thymidine incorporation assays.

Results: All BPH-tissues and, to a lesser degree, normal prostates, expressed significant amounts of IFN-gamma mRNA. However, only BPH-tissues contained IL-2 and IL-4 mRNA (ratio: 10:13). BPH-T-cell lines were heterogeneous in composition and expressed significant amounts of IFN-gamma, IL-2, and IL-4 mRNA. Low level expression of these lymphokines was also observed in BPH-EC, CaP lines, and PSC lines. IL-2, -7 and IFN-gamma stimulated the proliferation of BPH-PSC lines but not that of normal PSC, while IL-4 inhibited BPH-PSC growth.

Conclusions: Chronic inflammation may induce an increased growth pattern of fibromuscular tissue in BPH similar to that of wound healing.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Blotting, Southern
  • Cell Division*
  • Clone Cells / pathology
  • Cytokines / biosynthesis*
  • Cytokines / pharmacology
  • Gene Expression
  • Humans
  • Interferon-gamma / genetics
  • Interferon-gamma / pharmacology
  • Interleukin-2 / genetics
  • Interleukin-2 / pharmacology
  • Interleukin-4 / genetics
  • Interleukin-4 / pharmacology
  • Interleukin-7 / genetics
  • Interleukin-7 / pharmacology
  • Male
  • Phenotype
  • Prostatic Hyperplasia / metabolism*
  • Prostatic Hyperplasia / pathology
  • Prostatic Neoplasms
  • RNA, Messenger / analysis
  • Reverse Transcriptase Polymerase Chain Reaction
  • Stromal Cells / pathology*
  • T-Lymphocytes / metabolism*
  • Tumor Cells, Cultured

Substances

  • Cytokines
  • Interleukin-2
  • Interleukin-7
  • RNA, Messenger
  • Interleukin-4
  • Interferon-gamma