Organic dust activates NF- κB 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)- κB 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- κB 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- κB reporter gene in parallel with an increase in IL-6 and IL-8 release. The addition of pyrrolidinedithiocarbamate, a chemical NF- κB blocking agent, inhibited IL-6 and IL-8 secretion as well as the NF- κB reporter gene activity. Increasing the amount of I κB α led to inhibition of organic dust-induced IL-6 promoter and NF- κB reporter gene activities. Fluticasone inhibited the organic dust-induced NF- κB activation and IL-6 and IL-8 secretion. Finally, swine dust incubation of A549 cells resulted in a NF- κB DNA binding, which is composed of the NF- κB1 and RelA proteins. In conclusion, by interference at various levels we have shown that NF- κB plays a key role in the inflammatory response to organic dust.