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

128 Scopus citations


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
Issue number38
Publication statusPublished - Sep 20 2002


ASJC Scopus subject areas

  • Biochemistry

Cite this