Elucidation and control of mechanisms of mucus hypersecretion in the intractable upper airway diseases

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TGF-α immunoreactivity was found markedly increased in the submucosal tissue in the eosinophilic chronic rhinosinusitis patient compared with that of a normal patient and with noneosinophilic chronic rhinosinusitis. TGF-α synergized with TNF-α to upregulate MUC5AC expression in human epithelial cells through the ERK signaling pathway. IL-31 and IL-31RA are upregulated in patients with allergic rhinitis, and induce MUC5AC gene expression in human airway epithelial cells. These findings suggest that IL-31 plays an important role in mucus overproduction in nasal allergic inflammation. A new erythromycin derivative, EM900, does not have antibacterial action.EM900 suppressed induction of inflammatory cytokines and MUC5AC gene expression in cells derived from human airway epithelia, and our findings indicated that these effects may be mediated by the suppression of NF-κB activation.