Human neutrophil elastase-mediated goblet cell metaplasia is attenuated in TACE-deficient mice

Jin Ah Park, Asma S. Sharif, Tetsuya Shiomi, Lester Kobzik, David I. Kasahara, Daniel J. Tschumperlin, Judith Voynow, Jeffrey M. Drazen

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

Abstract

Neutrophilic inflammation is associated with chronic airway diseases. It has been observed that human neutrophil elastase (HNE), which is secreted by active neutrophils during inflammation, induces both mucin overproduction and goblet cell metaplasia. Several in vitro studies suggest that tumor necrosis factor-α converting enzyme (TACE) regulates the signaling axis that mediates HNE-induced mucin overproduction; however, it is unknown whether TACE performs a similar function in HNE-induced goblet cell metaplasia in vivo. We conducted this study to determine whether the inactivation of Tace gene expression attenuates HNE-induced goblet cell metaplasia in mice. Deletion of Tace is lethal shortly after birth in mice; therefore, we utilized Taceflox/floxR26CreER+/- mice and induced conditional deletion of Tace using a tamoxifen injection. Wild-type mice were given tamoxifen to control for its effect. Tace conditional deletion mice and wild-type mice were exposed to HNE via nasal instillation three times at 3-day intervals, and the lungs were harvested on day 11 after initial HNE exposure. Using periodic acid-Schiff staining and MUC5AC immunohistochemical staining to visualize goblet cells in the lungs, we found that HNE induced goblet cell metaplasia in the wild-type mice and that HNE-induced goblet cell metaplasia was significantly attenuated in the Tace conditional deletion mice. These findings suggest that TACE could be a potential target in the treatment of goblet cell metaplasia in patients with chronic airway diseases.

Original languageEnglish (US)
Pages (from-to)L701-L707
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume304
Issue number10
DOIs
StatePublished - 2013

Keywords

  • Airway epithelium
  • Airway mucin
  • Chronic airway disease
  • Neutrophilic inflammation

ASJC Scopus subject areas

  • Physiology
  • Pulmonary and Respiratory Medicine
  • Physiology (medical)
  • Cell Biology

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