Interleukin-9 upregulates mucus expression in the airways

被引:210
作者
Louahed, J
Toda, M
Jen, J
Hamid, Q
Renauld, JC
Levitt, RC
Nicolaides, NC
机构
[1] Magainin Pharmaceut Inc, Magainin Inst Mol Med, Plymouth Meeting, PA 19462 USA
[2] McGill Univ, Meakins Christie Labs, Montreal, PQ, Canada
[3] Johns Hopkins Univ, Med Dept Otolaryngol Head & Neck Surg & Oncol, Baltimore, MD USA
[4] Catholic Univ Louvain, Ludwig Inst Canc Res, B-1200 Brussels, Belgium
[5] Catholic Univ Louvain, Expt Med Unit, B-1200 Brussels, Belgium
关键词
D O I
10.1165/ajrcmb.22.6.3927
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Interleukin (IL)-9 has recently been shown to play an important role in allergic disease because its expression is strongly associated with the degree of airway responsiveness and the asthmatic-like phenotype, IL-9 is a pleiotropic cytokine that is active on many cell types involved in the allergic immune response, Mucus hypersecretion is a clinical feature of chronic airway diseases; however, the mechanisms underlying the induction of mucin are poorly understood. In this report, we show that IL-9 regulates the expression of a subset of mucin genes in lung cells both in vivo and in vitro. In vivo, the constitutive expression of IL-9 in transgenic mice results in elevated MUC2 and MUC5AC gene expression in airway epithelial cells and periodic acid-Schiff-positive staining (reflecting mucous glycogenates). Similar results were observed in C57BL/6J mice after IL-9 intratracheal instillation. In contrast, instillation of the T helper 1-associated cytokine interferon gamma failed to induce mucin production, In vitro, our studies showed that IL-9 also induces expression of MUC2 and MUC5AC in human primary lung cultures and in the human muccoepidermoid NCl-H292 cell line, indicating a direct 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 regulating the many clinical features of asthma and further supports the IL-9 pathway as a key mediator of the asthmatic response.
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收藏
页码:649 / 656
页数:8
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