Age-related increase in IL-17 activates pro-inflammatory signaling in prostate cells

Alejandra De Angulo, Robert Faris, Benjamin Daniel, Christopher Jolly, Linda DeGraffenried

Research output: Contribution to journalArticle

11 Scopus citations

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. Conclusion. Aging-mimic Tcell 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.

Original languageEnglish (US)
Pages (from-to)449-462
Number of pages14
JournalProstate
Volume75
Issue number5
DOIs
StatePublished - Apr 1 2015

Keywords

  • Aging
  • Inflammation
  • Interukin-17
  • T-lymphocytes

ASJC Scopus subject areas

  • Oncology
  • Urology

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    De Angulo, A., Faris, R., Daniel, B., Jolly, C., & DeGraffenried, L. (2015). Age-related increase in IL-17 activates pro-inflammatory signaling in prostate cells. Prostate, 75(5), 449-462. https://doi.org/10.1002/pros.22931