title: Age-related increase in IL-17 activates pro-inflammatory signaling in prostate cells.
abstract: BACKGROUND
  A close relationship between aging, inflammation, and prostate cancer is widely accepted. Aging is accompanied by a progressive increase in pro-inflammatory cytokines, including interleukin 17 (IL-17), a key pro-inflammatory cytokine that becomes dysregulated with age. However, the contribution of IL-17 to age-related prostate tumorigenesis remains unclear. The aim of this study was to investigate the role of age-related IL-17 dysregulation in prostate tumorigenesis.
  
  
  METHODS
  Serum and splenic T-lymphocytes from young GPAT-1 knock-out aging-mimic T cell mice as well as young and aged wild-type mice were collected. shRNA was used to knock down the IL-17 receptor in LNCaP prostate cancer cells and RWPE-1 non-transformed prostate epithelial cells, which were then exposed to the mouse sera or conditioned media from stimulated T-lymphocytes. NF-κB activation, NF-κB target gene expression, and cell proliferation were all measured in these cells by luciferase assay, qPCR, Western blot analysis, and MTT assay, respectively.
  
  
  RESULTS
  T-lymphocyte-secreted IL-17 from aging-mimic mice induced NF-κB activity and target gene expression in LNCaP and RWPE-1 cells. It also promoted proliferation of these cells.
  
  
  CONCLUSIONS
  Aging-mimic T cell mice produce increased levels of IL-17, which stimulates the pro-inflammatory NF-κB pathway in prostate epithelial cells. NF-κB increases inflammation, carcinogenesis and metastatic potential in the prostate. These findings provide evidence that the dysregulation of cytokine production seen in aged T cells may directly contribute to the increased risk for prostate cancer in the elderly.
authors.affiliation: Department of Nutritional Sciences, University of Texas at Austin, Austin, Texas.
authors.forename: Alejandra
authors.initials: A
authors.lastname: De Angulo
authors.forename: Robert
authors.initials: R
authors.lastname: Faris
authors.forename: Benjamin
authors.initials: B
authors.lastname: Daniel
authors.forename: Christopher
authors.initials: C
authors.lastname: Jolly
authors.forename: Linda
authors.initials: L
authors.lastname: deGraffenried
mesh_terms: D000375:Aging / Q000502:physiology*; D000818:Animals; D015153:Blotting, Western; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000473:pathology; D004847:Epithelial Cells / Q000378:metabolism; D006801:Humans; D020381:Interleukin-17 / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000378:metabolism*; D053722:Receptors, Interleukin-17 / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000502:physiology*; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D020381:Interleukin-17; D016328:NF-kappa B; D053722:Receptors, Interleukin-17
keywords: T-lymphocytes; aging; inflammation; interukin-17