Reduced Expression of GDF-15 is Associated with Atrophic Inflammatory Lesions of the Prostate

Overview

Journal Prostate

Date 2014 Oct 21

PMID 25327758

Citations 19

Authors

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

Affiliations

Soon will be listed here.

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.

Citing Articles

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Wan Y, Fu J Mol Cell Biochem. 2023; 479(3):453-466.

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The expression pattern of GDF15 in human brain changes during aging and in Alzheimer's disease.

Chiariello A, Valente S, Pasquinelli G, Baracca A, Sgarbi G, Solaini G Front Aging Neurosci. 2023; 14:1058665.

PMID: 36698863 PMC: 9869280. DOI: 10.3389/fnagi.2022.1058665.

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Bonaterra G, Schleper A, Skowronek M, Kilian L, Rink T, Schwarzbach H Cancers (Basel). 2022; 14(19).

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Ge R, Wang Z, Cheng L NPJ Precis Oncol. 2022; 6(1):31.

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