Reduced expression of GDF-15 is associated with atrophic inflammatory lesions of the prostate

Prostate. 2015 Feb 15;75(3):255-65. doi: 10.1002/pros.22911. Epub 2014 Oct 18.

Abstract

Background: Accumulating evidence suggests that chronic prostatic inflammation may lead to prostate cancer development. Growth differentiation factor-15 (GDF-15) is highly expressed in the prostate and has been associated with inflammation and tumorigenesis.

Methods: To examine the relationship between GDF-15 and prostatic inflammation, GDF-15 expression was measured by immunohistochemical (IHC) staining in human prostatectomy specimens containing inflammation. The relationship between GDF-15 and specific inflammatory cells was determined using non-biased computer image analysis. To provide insight into a potential suppressive role for GDF-15 in inflammation, activation of inflammatory mediator nuclear factor of kappa B (NFκB) was measured in PC3 cells.

Results: GDF-15 expression in luminal epithelial cells was decreased with increasing inflammation severity, suggesting an inverse association between GDF-15 and inflammation. Quantification of IHC staining by image analysis for GDF-15 and inflammatory cell markers revealed an inverse correlation between GDF-15 and CD3+, CD4+, CD8+, CD68+, and inos+ leukocytes. GDF-15 suppressed NFκB activity in luciferase reporter assays. Expression of the NFκB target, interleukin 8 (IL-8), was downregulated by GDF-15.

Conclusions: The inverse relationship between GDF-15 and inflammation demonstrates a novel expression pattern for GDF-15 in the human prostate and suppression of NFκB activity may shed light on a potential mechanism for this inverse correlation.

Keywords: GDF-15; NFκB; inflammation; macrophage.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, CD / metabolism
  • Atrophy / metabolism
  • Atrophy / pathology
  • Growth Differentiation Factor 15 / metabolism*
  • Humans
  • Male
  • NF-kappa B / metabolism*
  • Prostate / metabolism*
  • Prostate / pathology
  • Prostatitis / metabolism*
  • Prostatitis / pathology

Substances

  • Antigens, CD
  • Growth Differentiation Factor 15
  • NF-kappa B