title: Adenoviral E1A primes alveolar epithelial cells to PM(10)-induced transcription of interleukin-8.
abstract: The presence of the adenoviral early region 1A (E1A) protein in human lungs has been associated with an increased risk of chronic obstructive pulmonary disease (COPD), possibly by a mechanism involving amplification of proinflammatory responses. We hypothesize that enhanced inflammation results from increased transcription factor activation in E1A-carrying cells, which may afford susceptibility to environmental particulate matter < 10 microm (PM(10))-mediated oxidative stress. We measured interleukin (IL)-8 mRNA expression and protein release in human alveolar epithelial cells (A549) transfected with the E1A gene (E1A+ve). Both E1A+ve and -ve cells released IL-8 after incubation with TNF-alpha, but only E1A+ve cells were sensitive to LPS stimulation in IL-8 mRNA expression and protein release. E1A+ve cells showed an enhanced IL-8 mRNA and protein response after treatment with H(2)O(2) and PM(10). E1A-enhanced induction of IL-8 was accompanied by increases in activator protein-1 and nuclear factor-kappa B nuclear binding in E1A+ve cells, which also showed higher basal nuclear binding of these transcription factors. These data suggest that the presence of E1A primes the cell transcriptional machinery for oxidative stress signaling and therefore facilitates amplification of proinflammatory responses. By this mechanism, susceptibility to exacerbation of COPD in response to particulate air pollution may occur in individuals harboring E1A.
authors.affiliation: Respiratory Section, Edinburgh Lung and The Environment Group Initiative/Colt Laboratories, Department of Medical and Radiological Sciences, The University of Edinburgh Medical School, Edinburgh EH8 9AG, United Kingdom.
authors.forename: P S
authors.initials: PS
authors.lastname: Gilmour
authors.forename: I
authors.initials: I
authors.lastname: Rahman
authors.forename: S
authors.initials: S
authors.lastname: Hayashi
authors.forename: J C
authors.initials: JC
authors.lastname: Hogg
authors.forename: K
authors.initials: K
authors.lastname: Donaldson
authors.forename: W
authors.initials: W
authors.lastname: MacNee
mesh_terms: D017500:Adenovirus E1A Proteins / Q000494:pharmacology*; D000393:Air Pollutants / Q000494:pharmacology*; D022762:CCAAT-Enhancer-Binding Proteins / Q000378:metabolism; D002478:Cells, Cultured; D004357:Drug Synergism; D004847:Epithelial Cells / Q000187:drug effects; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D016209:Interleukin-8 / Q000235:genetics*; D008070:Lipopolysaccharides / Q000494:pharmacology; D016328:NF-kappa B / Q000378:metabolism; D010316:Particle Size; D011650:Pulmonary Alveoli / Q000166:cytology / Q000187:drug effects*; D012333:RNA, Messenger / Q000378:metabolism; D018808:Transcription Factor AP-1 / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D017500:Adenovirus E1A Proteins; D000393:Air Pollutants; D022762:CCAAT-Enhancer-Binding Proteins; D016209:Interleukin-8; D008070:Lipopolysaccharides; D016328:NF-kappa B; D012333:RNA, Messenger; D018808:Transcription Factor AP-1; D014409:Tumor Necrosis Factor-alpha