Interleukin-9 induces mucous cell metaplasia independent of inflammation

J. Rachel Reader, Dallas Melvin Hyde, Edward S. Schelegle, Melinda C. Aldrich, Amy M. Stoddard, Michael P. McLane, Roy C. Levitt, Jeffrey S. Tepper

Research output: Contribution to journalArticlepeer-review

61 Scopus citations


Interleukin-9 (IL-9) has been strongly implicated in the pathogenesis of asthma, including the overproduction of mucus, in humans and in animal models. We evaluated the inflammatory changes associated with the upregulation of mucus production by examining the time course of inflammation after daily intratracheal IL-9 administration to naive C57BI6 mice for 9 d. IL-9 induced an asthmatic phenotype, which in general took several days to develop, as assessed by the measurement of airway hyperresponsiveness, pulmonary inflammation, and serum immunoglobulin E. However, within 24 h of a single dose of IL-9, muc5ac mRNA upregulation occurred, and increased numbers of periodic acid Schiff/Alcian blue-positive mucous cells appeared. This response occurred before the development of an inflammatory cell influx and was the result of epithelial metaplasia. It seemed that IL-9 evoked mucous cell metaplasia independent of IL-13 because mRNA tissue evaluation indicated that muc5ac upregulation preceded any increase in IL-13 mRNA expression or detectable levels of IL-13 in the brochoalveolar lavage fluid. Therefore, the upregulation of IL-13 by IL-9 may be responsible for the amplification of mucus production but is not required for its initiation. IL-9 seems to directly stimulate mucous cell metaplasia without the requirement of inflammatory cell influx.

Original languageEnglish (US)
Pages (from-to)664-672
Number of pages9
JournalAmerican Journal of Respiratory Cell and Molecular Biology
Issue number6
StatePublished - Jun 1 2003

ASJC Scopus subject areas

  • Cell Biology
  • Pulmonary and Respiratory Medicine
  • Molecular Biology


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