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

与正常患者和非嗜酸性慢性鼻窦炎患者相比，嗜酸性慢性鼻窦炎患者粘膜下组织TGF-α免疫反应性明显增高。TGF-α与TNF-α协同通过ERK信号通路上调人上皮细胞MUC5AC的表达。IL-31和IL-31RA在变应性鼻炎患者中表达上调，诱导人气道上皮细胞MUC5AC基因表达。这些发现提示IL-31在鼻腔变应性炎症中粘液过量产生中起重要作用。一种新的红霉素衍生物EM900不具有抗菌作用。EM900可抑制人气道上皮细胞炎症因子的诱导和MUC5AC基因的表达，我们的研究结果表明，这些作用可能是通过抑制NF-κB的激活来介导的。

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.