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Published on: July 7, 2017
Chronic low-grade systemic inflammation causes DNA damage in the lungs of mice
Ken Arimura1, Kazutetsu Aoshiba, Takao Tsuji
1Pulmonary Division, Graduate School of Medical Science, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo, 162-8666, Japan.
Background:
Whether systemic inflammation compromises the pulmonary system is largely unknown. We tested the hypothesis that chronic low-grade systemic inflammation damages alveolar wall cells.
Methods:
A chronic low-grade systemic inflammatory state was induced in 8-week-old male C57/BL6J mice by administration of lipopolysaccharide (LPS, 44.4 μg/day) for a 90-day period by subcutaneous implantation of a delayed-release pellet system. Acute systemic inflammation was induced in another group of mice by a single intraperitoneal injection of LPS (125 μg/body). The lungs of mice were examined for histologic changes and genetic damage to alveolar wall cells.
Results:
Chronic LPS exposure for a 30-day period or a 90-day period did not cause any obvious architectural changes in the lungs except for a mild level of alveolar macrophage infiltration. Despite the lack of architectural changes in the lung, immunofluorescence staining for γH2AX and phosphorylated 53BP1 showed that chronic LPS exposure resulted in an almost doubling of the number of DNA double-strand breaks (DSBs) in type 1 and type 2 alveolar epithelial cells and in alveolar endothelial cells. Acute LPS exposure also resulted in a doubling of the number of DSBs in type 1 and type 2 alveolar epithelial cells and in alveolar endothelial cells at 24 h, but the increased number of DSBs returned to the baseline level by 48 h.
Conclusions:
These results suggest that chronic systemic low-grade inflammation induces persistent DNA damage in alveolar epithelial and endothelial cells before architectural changes in the lung become evident.
Insights
Chronic systemic inflammation causes DNA damage in lung cells before visible changes occur. This study reveals persistent DNA double-strand breaks in alveolar cells due to low-grade inflammation.
Area of Science:
- Pulmonary medicine
- Inflammation research
- Genotoxicology
Background:
- The impact of systemic inflammation on lung health is not well understood.
- This study investigates if chronic low-grade systemic inflammation damages alveolar wall cells.
Purpose of the Study:
- To determine if chronic low-grade systemic inflammation induces DNA damage in pulmonary alveolar cells.
- To assess the effects of both chronic and acute systemic inflammation on lung tissue.
Main Methods:
- Induced chronic low-grade systemic inflammation in mice using lipopolysaccharide (LPS) via sustained-release pellets for 90 days.
- Induced acute systemic inflammation with a single LPS injection.
- Examined lung histology and genetic damage (DNA double-strand breaks) in alveolar epithelial and endothelial cells.
Main Results:
- Chronic LPS exposure (30-90 days) did not cause significant lung architectural changes but doubled DNA double-strand breaks (DSBs) in alveolar epithelial and endothelial cells.
- Acute LPS exposure also doubled DSBs in these cells within 24 hours, with levels returning to baseline by 48 hours.
- Markers of DNA damage included γH2AX and phosphorylated 53BP1.
Conclusions:
- Chronic systemic inflammation leads to persistent DNA damage in alveolar epithelial and endothelial cells.
- This damage occurs prior to observable architectural alterations in the lung tissue.
- Suggests a potential mechanism for lung compromise under sustained inflammatory conditions.
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