Biomolecules 2015, 5(3), 1386-1398; doi:10.3390/biom5031386
Transcription of Interleukin-8: How Altered Regulation Can Affect Cystic Fibrosis Lung Disease
Department of Medicine, Respiratory Research Division, Royal College of Surgeons in Ireland Education and Research Centre, Beaumont Hospital, Dublin 9, Ireland
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Author to whom correspondence should be addressed.
Academic Editor: Ivana Vancurova
Received: 1 May 2015 / Revised: 19 June 2015 / Accepted: 20 June 2015 / Published: 1 July 2015
(This article belongs to the Special Issue Transcriptional Regulation of Pro-Inflammatory Genes)
Abstract
Interleukin-8 (IL-8) is a neutrophil chemokine that is encoded on the CXCL8 gene. Normally CXCL8 expression is repressed due to histone deacetylation, octamer-1 binding to the promoter and the inhibitory effect of nuclear factor-κB repressing factor (NRF). However, in response to a suitable stimulus, the human CXCL8 gene undergoes transcription due to its inducible promoter that is regulated by the transcription factors nuclear factor-κB (NF-κB), activating protein (AP-1), CAAT/enhancer-binding protein β (C/EBPβ, also known as NF-IL-6), C/EBP homologous protein (CHOP) and cAMP response element binding protein (CREB). CXCL8 mRNA is then stabilised by the activity of p38 mitogen-activated protein kinase (p38 MAPK). Cystic fibrosis (CF) lung disease is characterised by a neutrophil-dominated airway inflammatory response. A major factor contributing to the large number of neutrophils is the higher than normal levels of IL-8 that are present within the CF lung. Infection and inflammation, together with intrinsic alterations in CF airway cells are responsible for the abnormally high intrapulmonary levels of IL-8. Strategies to inhibit aberrantly high CXCL8 expression hold therapeutic potential for CF lung disease. View Full-TextKeywords:
interleukin-8; cystic fibrosis; lung
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).
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Jundi, K.; Greene, C.M. Transcription of Interleukin-8: How Altered Regulation Can Affect Cystic Fibrosis Lung Disease. Biomolecules 2015, 5, 1386-1398.
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