Interleukin-1beta Causes Pulmonary Inflammation, Emphysema, and Airway Remodeling in the Adult Murine Lung

Am J Respir Cell Mol Biol. 2005 Apr;32(4):311-8. doi: 10.1165/rcmb.2004-0309OC. Epub 2005 Jan 24.

Abstract

The production of the inflammatory cytokine interleukin (IL)-1 is increased in lungs of patients with chronic obstructive pulmonary disease (COPD) or asthma. To characterize the in vivo actions of IL-1 in the lung, transgenic mice were generated in which human IL-1beta was expressed in the lung epithelium with a doxycycline-inducible system controlled by the rat Clara cell secretory protein (CCSP) promoter. Induction of IL-1beta expression in the lungs of adult mice caused pulmonary inflammation characterized by neutrophil and macrophage infiltrates. IL-1beta caused distal airspace enlargement, consistent with emphysema. IL-1beta caused disruption of elastin fibers in alveolar septa and fibrosis in airway walls and in the pleura. IL-1beta increased the thickness of conducting airways, enhanced mucin production, and caused lymphocytic aggregates in the airways. Decreased immunostaining for the winged helix transcription factor FOXA2 was associated with goblet cell hyperplasia in IL-1beta-expressing mice. The production of the neutrophil attractant CXC chemokines KC (CXCL1) and MIP-2 (CXCL2), and of matrix metalloproteases MMP-9 and MMP-12, was increased by IL-1beta. Chronic production of IL-1beta in respiratory epithelial cells of adult mice causes lung inflammation, enlargement of distal airspaces, mucus metaplasia, and airway fibrosis in the adult mouse.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Asthma / etiology
  • Asthma / immunology
  • Asthma / pathology
  • Base Sequence
  • Bronchoalveolar Lavage Fluid / cytology
  • Bronchoalveolar Lavage Fluid / immunology
  • Chemokines, CXC / biosynthesis
  • Collagen / metabolism
  • DNA, Complementary / genetics
  • Disease Models, Animal
  • Elastin / metabolism
  • Gene Expression
  • Humans
  • Inflammation / etiology
  • Inflammation / immunology
  • Inflammation / pathology
  • Interleukin-1 / genetics
  • Interleukin-1 / physiology*
  • Lymphocytes / pathology
  • Matrix Metalloproteinases / biosynthesis
  • Mice
  • Mice, Transgenic
  • Organ Size
  • Organ Specificity
  • Pulmonary Disease, Chronic Obstructive / etiology*
  • Pulmonary Disease, Chronic Obstructive / immunology
  • Pulmonary Disease, Chronic Obstructive / pathology
  • Pulmonary Emphysema / etiology*
  • Pulmonary Emphysema / immunology
  • Pulmonary Emphysema / pathology
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Respiratory System / immunology
  • Respiratory System / pathology
  • Tumor Necrosis Factor-alpha / physiology

Substances

  • Chemokines, CXC
  • DNA, Complementary
  • Interleukin-1
  • RNA, Messenger
  • Tumor Necrosis Factor-alpha
  • Collagen
  • Elastin
  • Matrix Metalloproteinases