title: Aging affects lipopolysaccharide-induced upregulation of heme oxygenase-1 in the lungs and alveolar macrophages.
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.
authors.affiliation: First Department of Medicine, Hokkaido University School of Medicine, N-15, W-7, Kita-ku, Sapporo, 060-8638, Japan.
authors.forename: Yoko
authors.initials: Y
authors.lastname: Ito
authors.forename: Tomoko
authors.initials: T
authors.lastname: Betsuyaku
authors.forename: Chinatsu
authors.initials: C
authors.lastname: Moriyama
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Nasuhara
authors.forename: Masaharu
authors.initials: M
authors.lastname: Nishimura
mesh_terms: D055371:Acute Lung Injury / Q000139:chemically induced / Q000201:enzymology*; D000367:Age Factors; D000375:Aging / Q000378:metabolism*; D000818:Animals; D002478:Cells, Cultured; D004195:Disease Models, Animal; D015971:Gene Expression Regulation, Enzymologic; D051547:Heme Oxygenase-1 / Q000378:metabolism*; D008070:Lipopolysaccharides; D008168:Lung / Q000201:enzymology*; D016676:Macrophages, Alveolar / Q000201:enzymology*; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D008813:Mice, Inbred ICR; D012333:RNA, Messenger / Q000378:metabolism; D013997:Time Factors; D015854:Up-Regulation
chemical_list: D008070:Lipopolysaccharides; D008565:Membrane Proteins; D012333:RNA, Messenger; D051547:Heme Oxygenase-1; C496542:Hmox1 protein, mouse