Journal article
Role of repeated lung injury and genetic background in bleomycin-induced fibrosis
American journal of respiratory cell and molecular biology, Vol.29(3 Pt 1), pp.375-380
09/2003
DOI: 10.1165/rcmb.2003-0029oc
PMID: 12676806
Abstract
Current hypotheses of the pathogenesis of many forms of pulmonary fibrosis suggest that (i) a stimulus results in repeated or prolonged episodes of lung injury, and (ii) genetic factors modulate the outcome of the injury. The commonly employed single-exposure bleomycin model results in only temporary fibrosis. Therefore, we evaluated whether repeated bleomycin exposures, in the setting of a genetic background more likely to develop a T helper 2 (Th2) response, would induce prolonged fibrosis. Lung fibrosis was induced by intratracheal bleomycin injection, either as a single exposure or as three consecutive exposures. We found that bleomycin induced a Th2-like environment in both Th1-biased C57BL/6J and Th2-biased DBA/2 mice. We also found histologic changes and collagen increases consistent with lung injury/fibrosis at early time points, but prolonged fibrosis only after multiple exposures in the Th2-biased DBA/2 mice. We also determined if impaired healing of bleomycin-induced injury would prolong fibrosis in the C57BL/6J mice. Endothelial nitric oxide (which protects endothelial cells from oxidant-induced injury) synthase knockout animals on a C57BL/6J background also had prolonged fibrosis, similar to DBA/2 mice, after multiple bleomycin exposures. This was specific to eNOS, as inducible nitric oxide synthase knockout animals cleared the fibrosis as effectively as wild-type C57BL/6J mice. This data indicate that healing of injury/fibrosis after bleomycin is complex and can be determined by a number of genetic and environmental factors.
Details
- Title: Subtitle
- Role of repeated lung injury and genetic background in bleomycin-induced fibrosis
- Creators
- Man Pyo Chung - Division of Pulmonary and Critical Care Medicine, Department of Medicine, Samsung Medical Center, Sungkyunkwan University, Seoul, South KoreaMartha M MonickNabeel Y HamzehNoah S ButlerLinda S PowersGary W Hunninghake
- Resource Type
- Journal article
- Publication Details
- American journal of respiratory cell and molecular biology, Vol.29(3 Pt 1), pp.375-380
- Publisher
- United States
- DOI
- 10.1165/rcmb.2003-0029oc
- PMID
- 12676806
- ISSN
- 1044-1549
- eISSN
- 1535-4989
- Grant note
- HL-60316 / NHLBI NIH HHS ES-09607 / NIEHS NIH HHS
- Language
- English
- Date published
- 09/2003
- Academic Unit
- Microbiology and Immunology; Internal Medicine
- Record Identifier
- 9984001202502771
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