Faculty Collaboration Database

Reduced expression of GDF-15 is associated with atrophic inflammatory lesions of the prostate. Prostate 2015 Feb 15;75(3):255-65

Date

10/21/2014

Pubmed ID

25327758

Pubmed Central ID

PMC4682671

DOI

10.1002/pros.22911

Scopus ID

2-s2.0-84920740809 (requires institutional sign-in at Scopus site)   30 Citations

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.

Author List

Lambert JR, Whitson RJ, Iczkowski KA, La Rosa FG, Smith ML, Wilson RS, Smith EE, Torkko KC, Gari HH, Lucia MS

MESH terms used to index this publication - Major topics in bold

Antigens, CD
Atrophy
Growth Differentiation Factor 15
Humans
Male
NF-kappa B
Prostate
Prostatitis