Both canonical and non-canonical NF-κB activation contribute to the proliferative response of the middle ear mucosa during bacterial infection

A major aspect of pathology in otitis media (OM), the most common childhood bacterial disease, is hyperplasia of the middle ear mucosa. Activation of innate immune receptors during OM leads to the activation of NF-κB, a pleiotropic transcription factor involved both in inflammation and tissue growth. To explore the role of NF-κB in mucosal hyperplasia during OM, we evaluated the expression of genes involved in two modes of NF-κB activation during a complete episode of acute, bacterial OM in mice. We also determined the effects of inhibitors of each pathway on infection-stimulated mucosal growth in vitro. A majority of the genes that mediate both the canonical and the non-canonical pathways of NF-κB activation were regulated during OM, many with kinetics related to the time course of mucosal hyperplasia. Inhibition of either pathway reduced the growth of cultured mucosal explants in a dose-dependent manner. However, inhibition of the canonical pathway produced a greater effect, suggesting that this mode of NF-κB activation dominates mucosal hyperplasia during OM.