IL-13-induced Clara cell secretory protein expression in airway epithelium: Role of EGFR signaling pathway

Suil Kim, Jae Jeong Shim, Pierre Regis Burgel, Iris F. Ueki, Trang Dao-Pick, Dominic Cheng Wei Tam, Jay A. Nadel

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

Previous work showed that the Th2 cytokine interleukin (IL)-13 induces goblet cell metaplasia via an indirect mechanism involving the expression and subsequent activation of epidermal growth factor receptor (EGFR). Because Clara cell secretory protein (CCSP) expression has been reported in cells that express mucins, we examined the effect of IL-13 on CCSP gene and protein expression in pathogen-free rat airways and in pulmonary mucoepidermoid NCI-H292 cells. Intratracheal instillation of IL-13 induced CCSP mRNA in epithelial cells without cilia within 8-16 h, maximal between 24 and 48 h; CCSP immunostaining increased in a time-dependent fashion, maximal at 48 h. The CCSP immunostaining was localized in nongranulated secretory cells and goblet cells and in the lumen. Pretreatment with the selective EGFR tyrosine kinase inhibitor BIBX1522, cyclophosphamide (an inhibitor of bone marrow leukocyte mobilization), or a blocking antibody to IL-8 prevented CCSP staining. Treatment of NCI-H292 cells with the EGFR ligand transforming growth factor-α, but not with IL-13 alone, induced CCSP gene and protein expression. Selective EGFR tyrosine kinase inhibitors, BIBX1522 and AG1478, prevented CCSP expression in NCI-H292 cells, but the platelet-derived growth factor receptor tyrosine kinase inhibitor AG1295 had no effect. These findings indicate that IL-13 induces CCSP expression via an EGFR- and leukocyte-dependent pathway.

Original languageEnglish
Pages (from-to)L67-L75
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume283
Issue number1 27-1
DOIs
Publication statusPublished - 2002
Externally publishedYes

Keywords

  • Clara cell 10-kDa protein
  • Epidermal growth factor receptor
  • Goblet cell
  • Interleukin-13
  • Secretoglobin
  • Uteroglobin

ASJC Scopus subject areas

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

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