Interleukin-9 upregulates mucus expression in the airways

Jamila Louahed, Masao Toda, Jin Jen, Qutayba Hamid, Jean Cristophe Renauld, Roy C. Levitt, Nicholas C. Nicolaides

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Abstract

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 γ 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.

Original languageEnglish (US)
Pages (from-to)649-656
Number of pages8
JournalAmerican journal of respiratory cell and molecular biology
Volume22
Issue number6
DOIs
StatePublished - Jan 1 2000

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ASJC Scopus subject areas

  • Molecular Biology
  • Pulmonary and Respiratory Medicine
  • Clinical Biochemistry
  • Cell Biology

Cite this

Louahed, J., Toda, M., Jen, J., Hamid, Q., Renauld, J. C., Levitt, R. C., & Nicolaides, N. C. (2000). Interleukin-9 upregulates mucus expression in the airways. American journal of respiratory cell and molecular biology, 22(6), 649-656. https://doi.org/10.1165/ajrcmb.22.6.3927