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Interleukin-1β Causes Pulmonary Inflammation, Emphysema, and Airway Remodeling in the Adult Murine Lung
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.
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Vestbo, J., Hurd, S. S., Agustí, A. G., Jones, P. W., Vogelmeier, C., Anzueto, A., Barnes, P. J., Fabbri, L. M., Martinez, F. J., Nishimura, M., et al. (2013) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.201204-0596pp · Cited by 15,983
Piguet, P. F., Vesin, C., Grau, G. E., & Thompson, R. C. (1993) · Cytokine · doi:10.1016/1043-4666(93)90024-y · Cited by 215
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Araya, J., Cambier, S., Markovics, J. A., Wolters, P., Jablons, D., Hill, A., Finkbeiner, W., Jones, K., Broaddus, V. C., Sheppard, D., et al. (2007) · Journal of Clinical Investigation · doi:10.1172/jci32526 · Cited by 257
Metadata
- Authors
- Lappalainen, U., Whitsett, J. A., Wert, S. E., Tichelaar, J. W., & Bry, K.
- Venue
- American Journal of Respiratory Cell and Molecular Biology
- Publisher
- Oxford University Press (OUP)
- Published
- 2005-04
- Volume
- 32
- Issue
- 4
- Pages
- 311-318
- ISSN
- 1044-1549 (ISSN-L)
- 1535-4989
- OpenAlex
- W2144541431
- Cited by
- 430
- References
- 2
- FWCI
- 16.03
- Type
- journal article
- Language
- en
- Open access
- closed
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- CoChat. (2026). Citation check: Interleukin-1β Causes Pulmonary Inflammation, Emphysema, and Airway Remodeling in the Adult Murine Lung. https://app.cochat.ai/papers/10.1165/rcmb.2004-0309oc
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- Lappalainen, U., Whitsett, J. A., Wert, S. E., Tichelaar, J. W., & Bry, K. (2005). Interleukin-1β Causes Pulmonary Inflammation, Emphysema, and Airway Remodeling in the Adult Murine Lung. American Journal of Respiratory Cell and Molecular Biology. https://doi.org/10.1165/rcmb.2004-0309oc
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Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
