Interleukin-9 upregulates mucus expression in the airways

Interleukin (IL)-9 has recently been shown to play an important role in all ergic disease because its expression is strongly associated with the degree of airway responsiveness and the asthmatic-like phenotype, IL-9 is a pleio tropic cytokine that is active on many cell types involved in the allergic immune response, Mucus hypersecretion is a clinical feature of chronic airw ay diseases; however, the mechanisms underlying the induction of mucin are poorly understood. In this report, we show that IL-9 regulates the expressi on of a subset of mucin genes in lung cells both in vivo and in vitro. In v ivo, the constitutive expression of IL-9 in transgenic mice results in elev ated MUC2 and MUC5AC gene expression in airway epithelial cells and periodi c acid-Schiff-positive staining (reflecting mucous glycogenates). Similar r esults were observed in C57BL/6J mice after IL-9 intratracheal instillation . In contrast, instillation of the T helper 1-associated cytokine interfero n gamma failed to induce mucin production, In vitro, our studies showed tha t IL-9 also induces expression of MUC2 and MUC5AC in human primary lung cul tures and in the human muccoepidermoid NCl-H292 cell line, indicating a dir ect effect of IL-9 on inducing mucin expression in these cells. Altogether, these results suggest that upregulation of mucin by IL-9 might contribute to the pathogenesis of human inflammatory airway disorders, such as asthma. These data extend the role of the biologic processes that IL-9 has on regu lating the many clinical features of asthma and further supports the IL-9 p athway as a key mediator of the asthmatic response.