Expression of Beta-Defensin 131 Promotes an Innate Immune Response in Human Prostate Epithelial Cells.
Previously, using the Illumina HumanHT-12 microarray we found that β-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-...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2015-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC4674080?pdf=render |
| _version_ | 1818028534058188800 |
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| author | Jung Hoon Kim Kyeoung-Hwa Kim Hae Jong Kim Jaehyouk Lee Soon Chul Myung |
| author_facet | Jung Hoon Kim Kyeoung-Hwa Kim Hae Jong Kim Jaehyouk Lee Soon Chul Myung |
| author_sort | Jung Hoon Kim |
| collection | DOAJ |
| description | Previously, using the Illumina HumanHT-12 microarray we found that β-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-κB 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-κB activation, which was evident in the phosphorylation of both p38MAPK and IκBα. We also found that SB203580 and Bay11-7082, inhibitors of p38MAPK and NF-κB, respectively, suppressed LTA-induced DEFB131 expression. The chromatin immunoprecipitation assay showed that NF-κB directly binds to the DEFB131 promoter, suggesting that NF-κB 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-1α, IL-1β, IL-6, and IL-12α) 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-κB signaling pathway in RWPE-1 cells during bacterial infection and promotes an innate immune response. |
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| format | Article |
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| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-10T05:05:19Z |
| publishDate | 2015-01-01 |
| publisher | Public Library of Science (PLoS) |
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| series | PLoS ONE |
| spelling | doaj.art-a4f6c7d2bd1341db873c7fc987bc71f42022-12-22T02:01:16ZengPublic Library of Science (PLoS)PLoS ONE1932-62032015-01-011012e014477610.1371/journal.pone.0144776Expression of Beta-Defensin 131 Promotes an Innate Immune Response in Human Prostate Epithelial Cells.Jung Hoon KimKyeoung-Hwa KimHae Jong KimJaehyouk LeeSoon Chul MyungPreviously, using the Illumina HumanHT-12 microarray we found that β-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-κB 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-κB activation, which was evident in the phosphorylation of both p38MAPK and IκBα. We also found that SB203580 and Bay11-7082, inhibitors of p38MAPK and NF-κB, respectively, suppressed LTA-induced DEFB131 expression. The chromatin immunoprecipitation assay showed that NF-κB directly binds to the DEFB131 promoter, suggesting that NF-κB 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-1α, IL-1β, IL-6, and IL-12α) 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-κB signaling pathway in RWPE-1 cells during bacterial infection and promotes an innate immune response.http://europepmc.org/articles/PMC4674080?pdf=render |
| spellingShingle | Jung Hoon Kim Kyeoung-Hwa Kim Hae Jong Kim Jaehyouk Lee Soon Chul Myung Expression of Beta-Defensin 131 Promotes an Innate Immune Response in Human Prostate Epithelial Cells. PLoS ONE |
| title | Expression of Beta-Defensin 131 Promotes an Innate Immune Response in Human Prostate Epithelial Cells. |
| title_full | Expression of Beta-Defensin 131 Promotes an Innate Immune Response in Human Prostate Epithelial Cells. |
| title_fullStr | Expression of Beta-Defensin 131 Promotes an Innate Immune Response in Human Prostate Epithelial Cells. |
| title_full_unstemmed | Expression of Beta-Defensin 131 Promotes an Innate Immune Response in Human Prostate Epithelial Cells. |
| title_short | Expression of Beta-Defensin 131 Promotes an Innate Immune Response in Human Prostate Epithelial Cells. |
| title_sort | expression of beta defensin 131 promotes an innate immune response in human prostate epithelial cells |
| url | http://europepmc.org/articles/PMC4674080?pdf=render |
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