title: Transcription of Interleukin-8: How Altered Regulation Can Affect Cystic Fibrosis Lung Disease.
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.
authors.affiliation: Department of Medicine, Respiratory Research Division, Royal College of Surgeons in Ireland Education and Research Centre, Beaumont Hospital, Dublin 9, Ireland. karimjundi@rcsi.ie.
authors.forename: Karim
authors.initials: K
authors.lastname: Jundi
authors.affiliation: Department of Medicine, Respiratory Research Division, Royal College of Surgeons in Ireland Education and Research Centre, Beaumont Hospital, Dublin 9, Ireland. cmgreene@rcsi.ie.
authors.forename: Catherine M
authors.initials: CM
authors.lastname: Greene
mesh_terms: D000818:Animals; D003550:Cystic Fibrosis / Q000188:drug therapy / Q000235:genetics*; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D016209:Interleukin-8 / Q000235:genetics*; D008168:Lung / Q000187:drug effects / Q000378:metabolism; D058990:Molecular Targeted Therapy; D014158:Transcription, Genetic / Q000187:drug effects
chemical_list: D016209:Interleukin-8
keywords: cystic fibrosis; interleukin-8; lung