10779/rcsi.10785332.v1 Karim Jundi Karim Jundi Catherine M. Greene Catherine M. Greene Transcription of Interleukin-8: How Altered Regulation Can Affect Cystic Fibrosis Lung Disease. Royal College of Surgeons in Ireland 2019 Animals Cystic Fibrosis Gene Expression Regulation Humans Interleukin-8 Lung Molecular Targeted Therapy Transcription Genetic Medicine 2019-11-22 16:34:30 Journal contribution https://repository.rcsi.com/articles/journal_contribution/Transcription_of_Interleukin-8_How_Altered_Regulation_Can_Affect_Cystic_Fibrosis_Lung_Disease_/10785332 <p>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.</p>