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

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. Prostate 75:255–265, 2015. © 2014 Wiley Periodicals, Inc.