title: Reduced expression of GDF-15 is associated with atrophic inflammatory lesions of the prostate.
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.
authors.affiliation: Department of Pathology, University of Colorado Anschutz Medical Campus, Aurora, Colorado.
authors.forename: James R
authors.initials: JR
authors.lastname: Lambert
authors.forename: Ramon J
authors.initials: RJ
authors.lastname: Whitson
authors.forename: Kenneth A
authors.initials: KA
authors.lastname: Iczkowski
authors.forename: Francisco G
authors.initials: FG
authors.lastname: La Rosa
authors.forename: Maxwell L
authors.initials: ML
authors.lastname: Smith
authors.forename: R Storey
authors.initials: RS
authors.lastname: Wilson
authors.forename: Elizabeth E
authors.initials: EE
authors.lastname: Smith
authors.forename: Kathleen C
authors.initials: KC
authors.lastname: Torkko
authors.forename: Hamid H
authors.initials: HH
authors.lastname: Gari
authors.forename: M Scott
authors.initials: MS
authors.lastname: Lucia
mesh_terms: D015703:Antigens, CD / Q000378:metabolism; D001284:Atrophy / Q000378:metabolism / Q000473:pathology; D055436:Growth Differentiation Factor 15 / Q000378:metabolism*; D006801:Humans; D008297:Male; D016328:NF-kappa B / Q000378:metabolism*; D011467:Prostate / Q000378:metabolism* / Q000473:pathology; D011472:Prostatitis / Q000378:metabolism* / Q000473:pathology
chemical_list: D015703:Antigens, CD; D055436:Growth Differentiation Factor 15; D016328:NF-kappa B
keywords: GDF-15; NFκB; inflammation; macrophage