IL-4 Induces Mucin Gene Expression and Goblet Cell Metaplasia In Vitro and In Vivo

Goblet cell metaplasia and mucus hypersecretion are important features in the pathogenesis of asthma. The cytokine IL-4 has been shown to play a role in animal models of asthma, where it induces Th2 lymphocyte differentiation and B lymphocyte IgE class switch. IL-4 has also been implicated in the di...

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Bibliographic Details
Published in:The Journal of immunology (1950) 1999-05, Vol.162 (10), p.6233-6237
Main Authors: Dabbagh, Karim, Takeyama, Kiyoshi, Lee, Heung-Man, Ueki, Iris F, Lausier, James A, Nadel, Jay A
Format: Article
Language:English
Subjects:
Animals
Bronchi - drug effects
Bronchi - pathology
Bronchoalveolar Lavage Fluid - chemistry
Cell Line
Gene Expression Regulation
Glycoconjugates - biosynthesis
Goblet Cells - drug effects
Goblet Cells - pathology
Humans
Interleukin-1 - analysis
Interleukin-4 - pharmacology
Male
Metaplasia
Mice
Mice, Inbred BALB C
Mucin 5AC
Mucin-2
Mucins - biosynthesis
Mucins - genetics
Receptors, Interleukin-4 - isolation & purification
Tumor Necrosis Factor-alpha - analysis
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Summary:Goblet cell metaplasia and mucus hypersecretion are important features in the pathogenesis of asthma. The cytokine IL-4 has been shown to play a role in animal models of asthma, where it induces Th2 lymphocyte differentiation and B lymphocyte IgE class switch. IL-4 has also been implicated in the differentiation of goblet cells via effects on lymphocytes and eosinophils. In this study we hypothesized that IL-4 induces airway epithelial cell mucin gene expression and mucous glycoconjugate production by direct action on these cells. In vitro, cultured airway epithelial cells (NCI-H292) expressed IL-4R constitutively, and IL-4 (10 ng/ml) induced MUC2 gene expression and mucous glycoconjugate production. In vivo, mouse airway epithelial cells expressed IL-4R constitutively, and IL-4 (250 ng) increased MUC5 gene expression and Alcian blue/periodic acid-Schiff-positive staining at 24 h; IL-4 did not increase inflammatory cell numbers in airway tissue or in bronchoalveolar lavage. TNF-alpha and IL-1beta levels in bronchoalveolar lavage were not increased in response to IL-4 instillation. These results indicate that airway epithelial cells express IL-4R constitutively and that IL-4 directly induces the differentiation of epithelium into mucous glycoconjugate-containing goblet cells.
ISSN:0022-1767
1550-6606
DOI:10.4049/jimmunol.162.10.6233