title: Organic dust activates NF-kappaB in lung epithelial cells.
abstract: Exposure in swine confinement facilities induces airway inflammation in healthy subjects. The aim of the present study was to elucidate the role of nuclear factor (NF)-kappaB in the inflammatory response induced by organic dust. A human lung epithelial carcinoma cell line (A549) was transfected with reporter genes of the human IL-6 promoter or the NF-kappaB binding site fused to the luciferase reporter gene and stimulated with dust from a swine confinement building. Cytokine release in cell culture supernatants and luciferase activity was measured. The dust-induced the activities of the IL-6 promoter reporter gene and the NF-kappaB reporter gene in parallel with an increase in IL-6 and IL-8 release. The addition of pyrrolidinedithiocarbamate, a chemical NF-kappaB blocking agent, inhibited IL-6 and IL-8 secretion as well as the NF-kappaB reporter gene activity. Increasing the amount of IkappaB alpha led to inhibition of organic dust-induced IL-6 promoter and NF-kappaB reporter gene activities. Fluticasone inhibited the organic dust-induced NF-kappaB activation and IL-6 and IL-8 secretion. Finally, swine dust incubation of A549 cells resulted in a NF-kappaB DNA binding, which is composed of the NF-kappaB1 and RelA proteins. In conclusion, by interference at various levels we have shown that NF-kappaB plays a key role in the inflammatory response to organic dust.
authors.affiliation: Department of Medical Nutrition, Karolinska Institutet, Huddinge University Hospital Novum, Huddinge SE-141 86, Sweden.
authors.forename: Johan
authors.initials: J
authors.lastname: Lidén
authors.forename: Alexandra
authors.initials: A
authors.lastname: Ek
authors.forename: Lena
authors.initials: L
authors.lastname: Palmberg
authors.forename: Sam
authors.initials: S
authors.lastname: Okret
authors.forename: Kjell
authors.initials: K
authors.lastname: Larsson
mesh_terms: D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D004391:Dust; D004586:Electrophoresis; D004847:Epithelial Cells / Q000378:metabolism*; D000068298:Fluticasone; D017930:Genes, Reporter / Q000502:physiology; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D008156:Luciferases / Q000378:metabolism*; D008168:Lung / Q000166:cytology / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D013388:Succinimides / Q000494:pharmacology; D013552:Swine; D014162:Transfection; D014407:Tumor Cells, Cultured
chemical_list: D000730:Androstadienes; D000893:Anti-Inflammatory Agents; D004391:Dust; D015850:Interleukin-6; D016209:Interleukin-8; D016328:NF-kappa B; D013388:Succinimides; D000068298:Fluticasone; D008156:Luciferases