Expression of Beta-Defensin 131 Promotes an Innate Immune Response in Human Prostate Epithelial Cellsopen access
- Authors
- Kim, Jung Hoon; Kim, Kyeoung-Hwa; Kim, Hae Jong; Lee, Jaehyouk; Myung, Soon Chul
- Issue Date
- Dec-2015
- Publisher
- PUBLIC LIBRARY SCIENCE
- Citation
- PLOS ONE, v.10, no.12
- Journal Title
- PLOS ONE
- Volume
- 10
- Number
- 12
- URI
- https://scholarworks.bwise.kr/cau/handle/2019.sw.cau/8818
- DOI
- 10.1371/journal.pone.0144776
- ISSN
- 1932-6203
- Abstract
- Previously, using the Illumina HumanHT-12 microarray we found that beta-defensin 131 (DEFB131), an antimicrobial peptide, is upregulated in the human prostate epithelial cell line RWPE-1 upon stimulation with lipoteichoic acid (LTA; a gram-positive bacterial component), than that in the untreated RWPE-1 cells. In the current study, we aimed to investigate the role of DEFB131 in RWPE-1 cells during bacterial infection. We examined the intracellular signaling pathways and nuclear responses in RWPE-1 cells that contribute to DEFB131 gene induction upon stimulation with LTA. Chromatin immunoprecipitation was performed to determine whether NF-kappa B directly binds to the DEFB131 promoter after LTA stimulation in RWPE-1 cells. We found that DEFB131 expression was induced by LTA stimulation through TLR2 and p38MAPK/NF-kappa B activation, which was evident in the phosphorylation of both p38MAPK and I kappa B alpha. We also found that SB203580 and Bay11-7082, inhibitors of p38MAPK and NF-kappa B, respectively, suppressed LTA-induced DEFB131 expression. The chromatin immunoprecipitation assay showed that NF-kappa B directly binds to the DEFB131 promoter, suggesting that NF-kappa B is a direct regulator, and is necessary for LTA-induced DEFB131 expression in RWPE-1 cells. Interestingly, with DEFB131 overexpression in RWPE-1 cells, the accumulation of mRNA and protein secretion of cytokines (IL-1 alpha, IL-1 beta, IL-6, and IL-12 alpha) and chemokines (CCL20, CCL22, and CXCL8) were significantly enhanced. In addition, DEFB131-transfected RWPE-1 cells markedly induced chemotactic activity in THP-1 monocytes. We concluded that DEFB131 induces cytokine and chemokine upregulation through the TLR2/NF-kappa B signaling pathway in RWPE-1 cells during bacterial infection and promotes an innate immune response.
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