Transgenic overexpression of interleukin (IL)-10 in the lung causes mucus metaplasia, tissue inflammation, and airway remodeling via IL-13-dependent and -independent pathways

Chun Geun Lee, Robert J. Homer, Lauren Cohn, Holger Link, Sungsoo Jung, Joseph E. Craft, Barney S. Graham, Teresa R. Johnson, Jack A. Elias

Research output: Contribution to journalArticle

125 Citations (Scopus)

Abstract

To address the complex chronic effector properties of interleukin (IL)-10, we generated transgenic mice in which IL-10 was overexpressed in the lung. In these mice, IL-10 inhibited endotoxin-induced tumor necrosis factor production and neutrophil accumulation. IL-10 also caused mucus metaplasia, B and T cell-rich inflammation, and subepithelial fibrosis and augmented the levels of mRNA encoding Gob-5, mucins, and IL-13. In mice bred to have null mutations of IL-13, IL-4Ra, or STAT-6, transgenic IL-10 did not induce mucus metaplasia but did induce inflammation and fibrosis. IL-10 was also a critical mucin regulator of virus-induced mucus metaplasia. Thus, IL-10, although inhibiting lipopolysaccharide-induced inflammation, also causes mucus metaplasia, tissue inflammation, and airway fibrosis. These responses are mediated by multiple mechanisms with mucus metaplasia being dependent on and the inflammation and fibrosis being independent of an IL-13/IL-4Rα/STAT-6 activation pathway.

Original languageEnglish (US)
Pages (from-to)35466-35474
Number of pages9
JournalJournal of Biological Chemistry
Volume277
Issue number38
DOIs
StatePublished - Sep 20 2002

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Airway Remodeling
Interleukin-13
Metaplasia
Mucus
Interleukin-10
Tissue
Inflammation
Lung
Fibrosis
Interleukins
Mucins
T-cells
Viruses
Endotoxins
Transgenic Mice
Lipopolysaccharides
Neutrophils
B-Lymphocytes
Tumor Necrosis Factor-alpha
Chemical activation

ASJC Scopus subject areas

  • Biochemistry

Cite this

Transgenic overexpression of interleukin (IL)-10 in the lung causes mucus metaplasia, tissue inflammation, and airway remodeling via IL-13-dependent and -independent pathways. / Lee, Chun Geun; Homer, Robert J.; Cohn, Lauren; Link, Holger; Jung, Sungsoo; Craft, Joseph E.; Graham, Barney S.; Johnson, Teresa R.; Elias, Jack A.

In: Journal of Biological Chemistry, Vol. 277, No. 38, 20.09.2002, p. 35466-35474.

Research output: Contribution to journalArticle

Lee, Chun Geun ; Homer, Robert J. ; Cohn, Lauren ; Link, Holger ; Jung, Sungsoo ; Craft, Joseph E. ; Graham, Barney S. ; Johnson, Teresa R. ; Elias, Jack A. / Transgenic overexpression of interleukin (IL)-10 in the lung causes mucus metaplasia, tissue inflammation, and airway remodeling via IL-13-dependent and -independent pathways. In: Journal of Biological Chemistry. 2002 ; Vol. 277, No. 38. pp. 35466-35474.
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AU - Cohn, Lauren

AU - Link, Holger

AU - Jung, Sungsoo

AU - Craft, Joseph E.

AU - Graham, Barney S.

AU - Johnson, Teresa R.

AU - Elias, Jack A.

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