Interleukin-9 upregulates mucus expression in the airways.
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 NCI-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.
Louahed
J
J
Magainin Institute of Molecular Medicine, Magainin Pharmaceuticals, Inc., Plymouth Meeting, Pennsylvania 19462, USA.
Toda
M
M
Jen
J
J
Hamid
Q
Q
Renauld
J C
JC
Levitt
R C
RC
Nicolaides
N C
NC
D000818:Animals; D001249:Asthma / Q000276:immunology / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell; D017931:DNA Primers; D004847:Epithelial Cells / Q000276:immunology / Q000378:metabolism; D015870:Gene Expression / Q000276:immunology; D006023:Glycoproteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D020397:Goblet Cells / Q000276:immunology / Q000378:metabolism; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology / Q000378:metabolism*; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D018793:Interleukin-13 / Q000276:immunology / Q000378:metabolism; D016906:Interleukin-9 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D008168:Lung / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D055271:Mucin 5AC; D055262:Mucin-2; D009077:Mucins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D009093:Mucus / Q000276:immunology / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D020545:Respiratory Mucosa / Q000276:immunology / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D017931:DNA Primers; D006023:Glycoproteins; D018793:Interleukin-13; D016906:Interleukin-9; C524625:MUC2 protein, human; C524678:MUC5AC protein, human; C524626:Muc2 protein, mouse; C524679:Muc5ac protein, mouse; D055271:Mucin 5AC; D055262:Mucin-2; D009077:Mucins; D007371:Interferon-gamma