Superinduction of NF-kappa B by actinomycin D and cycloheximide in epithelial cells.

Epithelial cells are actively involved in inflammation and play a role in inflammatory diseases such as asthma. Numerous proinflammatory genes, expressed in the airway epithelium, are regulated by the transcription factor NF-kappa B. We show that the proinflammatory cytokines, IL-1 beta and TNF alpha, as well as a protein kinase C activator cause NF-kappa B activation in A549 epithelial cells. This observation is consistent with a major role for NF-kappa B in inflammation. We also demonstrate that IL-1 beta costimulation with a protein synthesis inhibitor, cycloheximide, or a transcription blocker, actinomycin D, results in superinduction of NF-kappa B but not the transcription factors Oct 1, AP-1, and Sp-1. We speculate that this may be due to lack of de novo synthesis of the NF-kappa B inhibitor, I kappa B alpha, and suggest that this phenomena may help explain the widely observed effect of mRNA superinduction of primary response genes in response to translational blockers.