Epigenetic dysregulation of interleukin 8 (CXCL8) hypersecretion in cystic fibrosis airway epithelial cells
Airway epithelial cells in cystic fibrosis (CF) overexpress Interleukin 8 (CXCL8) through poorly defined mechanisms. CXCL8 transcription is dependent on coordinated binding of CCAAT/enhancer binding protein (C/EBP)β, nuclear factor (NF)-κB, and activator protein (AP)-1 to the promoter. Here we show...
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| Format: | Article |
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Elsevier
2016
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| Online Access: | https://eprints.nottingham.ac.uk/48678/ |
| _version_ | 1848797820886188032 |
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| author | Poghosyan, Anna Patel, Jamie K. Clifford, Rachel L. Knox, Alan J. |
| author_facet | Poghosyan, Anna Patel, Jamie K. Clifford, Rachel L. Knox, Alan J. |
| author_sort | Poghosyan, Anna |
| building | Nottingham Research Data Repository |
| collection | Online Access |
| description | Airway epithelial cells in cystic fibrosis (CF) overexpress Interleukin 8 (CXCL8) through poorly defined mechanisms. CXCL8 transcription is dependent on coordinated binding of CCAAT/enhancer binding protein (C/EBP)β, nuclear factor (NF)-κB, and activator protein (AP)-1 to the promoter. Here we show abnormal epigenetic regulation is responsible for CXCL8 overexpression in CF cells. Under basal conditions CF cells had increased bromodomain (Brd)3 and Brd4 recruitment and enhanced NF-κB and C/EBPβ binding to the CXCL8 promoter compared to non-CF cells due to trimethylation of histone H3 at lysine 4 (H3K4me3) and DNA hypomethylation at CpG6. IL-1β increased NF-κB, C/EBPβ and Brd4 binding. Furthermore, inhibitors of bromodomain and extra-terminal domain family (BET) proteins reduced CXCL8 production in CF cells suggesting a therapeutic target for the BET pathway. |
| first_indexed | 2025-11-14T20:09:57Z |
| format | Article |
| id | nottingham-48678 |
| institution | University of Nottingham Malaysia Campus |
| institution_category | Local University |
| last_indexed | 2025-11-14T20:09:57Z |
| publishDate | 2016 |
| publisher | Elsevier |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | nottingham-486782020-05-04T18:07:43Z https://eprints.nottingham.ac.uk/48678/ Epigenetic dysregulation of interleukin 8 (CXCL8) hypersecretion in cystic fibrosis airway epithelial cells Poghosyan, Anna Patel, Jamie K. Clifford, Rachel L. Knox, Alan J. Airway epithelial cells in cystic fibrosis (CF) overexpress Interleukin 8 (CXCL8) through poorly defined mechanisms. CXCL8 transcription is dependent on coordinated binding of CCAAT/enhancer binding protein (C/EBP)β, nuclear factor (NF)-κB, and activator protein (AP)-1 to the promoter. Here we show abnormal epigenetic regulation is responsible for CXCL8 overexpression in CF cells. Under basal conditions CF cells had increased bromodomain (Brd)3 and Brd4 recruitment and enhanced NF-κB and C/EBPβ binding to the CXCL8 promoter compared to non-CF cells due to trimethylation of histone H3 at lysine 4 (H3K4me3) and DNA hypomethylation at CpG6. IL-1β increased NF-κB, C/EBPβ and Brd4 binding. Furthermore, inhibitors of bromodomain and extra-terminal domain family (BET) proteins reduced CXCL8 production in CF cells suggesting a therapeutic target for the BET pathway. Elsevier 2016-08-05 Article PeerReviewed Poghosyan, Anna, Patel, Jamie K., Clifford, Rachel L. and Knox, Alan J. (2016) Epigenetic dysregulation of interleukin 8 (CXCL8) hypersecretion in cystic fibrosis airway epithelial cells. Biochemical and Biophysical Research Communications, 476 (4). pp. 431-437. ISSN 1090-2104 CF; Epigenetics; CXCL8; BRD4 http://www.sciencedirect.com/science/article/pii/S0006291X16308622 doi:10.1016/j.bbrc.2016.05.140 doi:10.1016/j.bbrc.2016.05.140 |
| spellingShingle | CF; Epigenetics; CXCL8; BRD4 Poghosyan, Anna Patel, Jamie K. Clifford, Rachel L. Knox, Alan J. Epigenetic dysregulation of interleukin 8 (CXCL8) hypersecretion in cystic fibrosis airway epithelial cells |
| title | Epigenetic dysregulation of interleukin 8 (CXCL8) hypersecretion in cystic fibrosis airway epithelial cells |
| title_full | Epigenetic dysregulation of interleukin 8 (CXCL8) hypersecretion in cystic fibrosis airway epithelial cells |
| title_fullStr | Epigenetic dysregulation of interleukin 8 (CXCL8) hypersecretion in cystic fibrosis airway epithelial cells |
| title_full_unstemmed | Epigenetic dysregulation of interleukin 8 (CXCL8) hypersecretion in cystic fibrosis airway epithelial cells |
| title_short | Epigenetic dysregulation of interleukin 8 (CXCL8) hypersecretion in cystic fibrosis airway epithelial cells |
| title_sort | epigenetic dysregulation of interleukin 8 (cxcl8) hypersecretion in cystic fibrosis airway epithelial cells |
| topic | CF; Epigenetics; CXCL8; BRD4 |
| url | https://eprints.nottingham.ac.uk/48678/ https://eprints.nottingham.ac.uk/48678/ https://eprints.nottingham.ac.uk/48678/ |