Targeted expression of IL-11 in the murine airway causes lymphocytic inflammation, bronchial remodeling, and airways obstruction

Weiliang Tang, Gregory P. Geba, Tao Zheng, Prabir Ray, Robert J. Homer, Charles Kuhn, Richard A. Flavell, Jack A. Elias

Research output: Contribution to journalArticlepeer-review

Abstract

Interleukin-11 is a pleotropic cytokine produced by lung stromal cells in response to respiratory viruses, cytokines, and histamine. To further define its potential effector functions, the Clara cell 10-kD protein promoter was used to express IL-11 and the airways of the resulting transgene mice were characterized. In contrast to transgene (-) littermates, the airways of IL-11 transgene (+) animals manifest nodular peribronchiolar mononuclear cell infiltrates and impressive airways remodeling with subepithelial fibrosis. The inflammatory loci contained large numbers of B220(+) and MHC Class II(+) cells and lesser numbers of CD3(+), CD4(+), and CD8(+) cells. The fibrotic response contained increased amounts of types III and I collagen, increased numbers of α smooth muscle actin and desrain- containing cells and a spectrum of stromal elements including fibroblasts, myofibroblasts, and smooth muscle cells. Physiologic evaluation also demonstrated that 2-too-old transgene (+) mice had increased airways resistance and non-specific airways hyperresponsiveness to methacholine when compared with their transgene (-) littermates. These studies demonstrate that the targeted expression of IL-II in the mouse airway causes a B and T cell- predominant inflammatory response, airway remodeling with increased types III and I collagen, the local accumulation of fibroblasts, myofibroblasts, and myocytes, and obstructive physiologic dysregulation. IL-11 may play an important role in the inflammatory and fibrotic responses in viral and/or nonvital human airway disorders.

Original languageEnglish (US)
Pages (from-to)2845-2853
Number of pages9
JournalJournal of Clinical Investigation
Volume98
Issue number12
DOIs
StatePublished - Dec 15 1996

Keywords

  • collagen
  • cytokine
  • epithelial cell
  • fibrosis
  • myofibroblast

ASJC Scopus subject areas

  • Medicine(all)

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