Interleukin-1β causes pulmonary inflammation, emphysema, and airway remodeling in the adult murine lung

被引:341
作者
Lappalainen, U
Whitsett, JA
Wert, SE
Tichelaar, JW
Bry, K
机构
[1] Univ Gothenburg, Dept Pediat, Gothenburg, Sweden
[2] Childrens Hosp, Med Ctr, Div Neonatol, Cincinnati, OH 45229 USA
[3] Childrens Hosp, Med Ctr, Div Pulm Biol, Cincinnati, OH 45229 USA
[4] Univ Cincinnati, Dept Environm Hlth, Cincinnati, OH USA
关键词
cytokine; asthma; chronic obstructive pulmonary disease; metalloprotease; neutrophil;
D O I
10.1165/rcmb.2004-0309OC
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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-1 beta was expressed in the lung epithelium with a doxycycline-inducible system controlled by the rat Clara cell secretory protein (CCSP) promoter. Induction of IL-1 beta expression in the lungs of adult mice caused pulmonary inflammation characterized by neutrophil and macrophage infiltrates. IL-1 beta caused distal airspace enlargement, consistent with emphysema. IL-1 beta caused disruption of elastin fibers in alveolar septa and fibrosis in airway walls and in the pleura. IL-1 beta 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-I beta-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-1 beta. Chronic production of IL-1 beta in respiratory epithelial cells of adult mice causes lung inflammation, enlargement of distal airspaces, mucus metaplasia, and airway fibrosis in the adult mouse.
引用
收藏
页码:311 / 318
页数:8
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