IL-1β induces IL-8 in bronchial cells via NF-κB and NF-IL6 transcription factors and can be suppressed by glucocorticoids

Abstract

IL-1β may contribute to airway inflammation by inducing pro-inflammatory cytokines and chemokines from bronchial epithelial cells. In the current study, we investigated the cis-acting sites within the IL-8 promoter, and signalling pathways important in IL-8 production from BEAS2B cells following IL-1β stimulation. IL-1β treatment (0.1–10 ng/mL) upregulated IL-8 protein production in a dose dependent manner and IL-8 mRNA in a time dependent manner. IL-1β induced upregulation of IL-8 promoter-reporter constructs, indicating that the mechanism of upregulation was pre-transcriptional. Using IL-8 promoter constructs with mutated cis-acting sites, it was found that both the NF-κB and NF-IL6 sites together were required for IL-8 promoter induction following IL-1β treatment. Using chemical inhibitors or dominant negative mutants, we found that IL-8 promoter activity required IκB kinase β, IκB, but not the MAP kinases p38 or c-Jun N-terminal kinase 2. Fluticasone propionate was able to suppress IL-1β induced IL-8 protein and promoter activation, using both a −1481 bp fragment and a −133 bp fragment, indicating that the glucocorticoid response element found at −330 bp was not required for fluticasone mediated suppression of IL-8 promoter activation.