インテグリン不活性化ペプチドFNIII14は気道上皮細胞のMUC5AC分泌を抑制する。

抄録

Airway mucus hypersecretion is a hallmark of respiratory diseases. Recently, several reports showed that the extracellular microenvironment regulates mucus hypersecretion; however, its underlining mechanism is not well understood. Therefore, we examined the effect of FNIII14, an integrin inactivating peptide, on the production and secretion of MUC5AC, a major component of airway mucin. In this study, NCI-H292 cells, goblet-like mucus producing cells, were treated with TGF-α to induce the production of MUC5AC. Co-treatment of FNIII14 with TGF-α for 12 or 24 h did not affect TGF-α-induced MUC5AC mRNA expression. However, FNIII14 markedly suppressed MUC5AC protein level in the culture supernatant, whereas intracellular pool of MUC5AC was increased. FNIII14 also decreased MUC5AC secretion induced by ionomycin, suggesting that integrins plays important role in both spontaneous and regulated secretory process of MUC5AC. Furthermore, an inhibitor of integrin downstream signaling molecule FAK (Y15), as well as FNIII14, inhibited MUC5AC secretion. These data suggested that interaction between integrin and extracellular matrix and activation of FAK are required to obtain MUC5AC secretory property in goblet cells. These data may also provide new strategy to regulate mucus hypersecretion in airway diseases.