Document Type

Article

Publication Date

1-7-2015

Keywords

Animals, Cystic Fibrosis, Gene Expression Regulation, Humans, Interleukin-8, Lung, Molecular Targeted Therapy, Transcription, Genetic

Funder/Sponsor

Science Foundation Ireland, National Children’s Research Centre, Royal College of Surgeons in Ireland, European Respiratory Society.

Comments

The original article is available at http://www.mdpi.com/

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.

Disciplines

Medicine and Health Sciences

Citation

Jundi K, Greene CM. Transcription of Interleukin-8: How Altered Regulation Can Affect Cystic Fibrosis Lung Disease. Biomolecules. 2015;5(3):1386-98.

PubMed ID

26140537

DOI Link

10.3390/biom5031386

Creative Commons License

Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-Share Alike 4.0 License.

Share

COinS