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Abstract Title:

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

Abstract Source:

Prostate. 2014 Oct 18. Epub 2014 Oct 18. PMID: 25327758

Abstract Author(s):

James R Lambert, Ramon J Whitson, Kenneth A Iczkowski, Francisco G La Rosa, Maxwell L Smith, R Storey Wilson, Elizabeth E Smith, Kathleen C Torkko, Hamid H Gari, M Scott Lucia

Article Affiliation:

James R Lambert

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. Prostate © 2014 Wiley Periodicals, Inc.

Study Type : Animal Study, Human In Vitro

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