German Cockroach Proteases Regulate Interleukin-8 Expression via Nuclear Factor for Interleukin-6 in Human Bronchial Epithelial Cells

German cockroach extract synergistically regulates tumor necrosis factor-α (TNF-α)–induced interleukin (IL)-8 expression in human airway epithelial cells. The IL-8 promoter contains nuclear factor (NF)-κB, activating protein (AP)-1, and NF for IL-6 (NF-IL6) transcription factor binding regions. Because cockroach extract activates extracellular regulated kinase (ERK), a known activator of AP-1 and NF-IL6, we focused on the regulation of these transcription factors. Although TNF-α and cockroach extract both increased AP-1 translocation, mutation of the AP-1 site in the context of the wild-type promoter had no effect on cockroach extract–induced synergy. Mutation of the NF-IL6 site in the context of the wild-type IL-8 promoter, or overexpression of a dominant-negative NF-IL6 mutant, each abolished cockroach extract–induced synergy. Cockroach extract induced NF-IL6 translocation and DNA binding, an effect that was further increased in the presence of TNF-α. Cockroach extract–induced regulation of NF-IL6 was d...