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
Date
01/26/2005Pubmed ID
15668323DOI
10.1165/rcmb.2004-0309OCScopus ID
2-s2.0-16444377075 (requires institutional sign-in at Scopus site) 392 CitationsAbstract
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.
Author List
Lappalainen U, Whitsett JA, Wert SE, Tichelaar JW, Bry KMESH terms used to index this publication - Major topics in bold
AnimalsAsthma
Base Sequence
Bronchoalveolar Lavage Fluid
Chemokines, CXC
Collagen
DNA, Complementary
Disease Models, Animal
Elastin
Gene Expression
Humans
Inflammation
Interleukin-1
Lymphocytes
Matrix Metalloproteinases
Mice
Mice, Transgenic
Organ Size
Organ Specificity
Pulmonary Disease, Chronic Obstructive
Pulmonary Emphysema
RNA, Messenger
Respiratory System
Tumor Necrosis Factor-alpha
