Abstract
Lung injuries are generally more serious and cause high mortality in aged humans and animals. Heme Oxygenase-1 (HO-1) is known to be readily inducible in alveolar macrophages (AMs) and airway epithelial cells to confer cytoprotection against oxidative stress. We thus investigated whether aging impairs the stress-induced upregulation of HO-1. In this study, we first quantified basal levels of HO-1 expression in lungs from male ICR mice of various ages. Second, young (9–11 weeks) and old (65–66 weeks) mice were subjected to intratracheal administration of lipopolysaccharide (LPS) and expression of HO-1 in the lungs was quantified at 2, 24 and 72 h. HO-1 expression in bronchiolar epithelial cells harvested by laser capture microdissection (LCM) was also specifically quantified in the two age groups. Third, we examined HO-1 expression in AMs lavaged from 22-week-old and 86–96-week-old male ICR mice in response to LPS for 24 h in vitro. We found that basal expression of HO-1 in the lungs did not differ with age. LPS-induced HO-1 upregulation was significantly impaired in the lungs of 65–66-week-old mice than in 9–11-week-old mice at 2 and 24 h, although there were no differences in the magnitude of HO-1 upregulation in bronchiolar epithelium at 2 h. LPS-induced upregulation of HO-1 was observed in AMs from 22-week-old mice (1.8-fold), but not in AMs from 86–96-week-old mice in vitro. In summary, we demonstrated age-related defects in HO-1 induction in the whole lungs and in AMs in response to LPS.
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Abbreviations
- AMs:
-
Alveolar macrophages
- ARDS:
-
Acute respiratory distress syndrome
- BAL:
-
Bronchoalveolar lavage
- β2MG:
-
β2-Microglobulin
- BGUS:
-
β-Glucuronidase
- HO-1:
-
Heme oxygenase-1
- HPRT:
-
Hypoxanthine ribosyltransferase
- LPS:
-
Lipopolysaccharide
- LCM:
-
Laser capture microdissection
- Nrf2:
-
Nuclear factor erythroid 2-related factor
- PCR:
-
Polymerase chain reaction
- SE:
-
Standard error
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Acknowledgements
This research was supported by a scientific research grant from the Ministry of Education, Culture, Sports, Science and Technology of Japan (No. 19590877 to T.B.). The authors would like to thank Ms. Yoko Suzuki for her invaluable technical assistance.
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Ito, Y., Betsuyaku, T., Moriyama, C. et al. Aging affects lipopolysaccharide-induced upregulation of heme oxygenase-1 in the lungs and alveolar macrophages. Biogerontology 10, 173–180 (2009). https://doi.org/10.1007/s10522-008-9164-4
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DOI: https://doi.org/10.1007/s10522-008-9164-4