科研之友
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摘要
BackgroundA 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. MethodsSerum 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-B activation, NF-B target gene expression, and cell proliferation were all measured in these cells by luciferase assay, qPCR, Western blot analysis, and MTT assay, respectively. ResultsT-lymphocyte-secreted IL-17 from aging-mimic mice induced NF-B activity and target gene expression in LNCaP and RWPE-1 cells. It also promoted proliferation of these cells. ConclusionAging-mimic T cell mice produce increased levels of IL-17, which stimulates the pro-inflammatory NF-B pathway in prostate epithelial cells. NF-B 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. Prostate 75: 449-462, 2015.
- 出版日期2015-4-1
