title: Aging enhances susceptibility to cigarette smoke-induced inflammation through bronchiolar chemokines.
abstract: Cigarette smoking and aging are major risk factors for chronic obstructive pulmonary disease. An unsolved question is whether elderly lungs are particularly vulnerable to cigarette smoke (CS) exposure. In this study, we used a mouse model to test the hypothesis that aging increases the susceptibility to CS-induced pulmonary inflammation. We subjected 9-week-old and 69-week-old C57BL/6J mice to CS (whole-body exposure, 90 min/d), and evaluated neutrophil infiltration in the lungs, the levels of keratinocyte-derived chemokine (KC) and macrophage inflammatory protein (MIP)-2 in bronchoalveolar lavage fluid, and mRNA expression in bronchiolar epithelium retrieved by laser capture microdissection. The 69-week-old mice showed a greater number of neutrophils and higher levels of bronchiolar KC and MIP-2 expression than 9-week-old mice after 9 days of CS exposure. Furthermore, single CS exposure induced the rapid up-regulation of KC and MIP-2 in bronchiolar epithelium in both 9-week-old and 69-week-old mice, and the much higher levels in 69-week-old mice were associated with greater nuclear translocation of NF-kappaB. In contrast, no age-related differences were observed in the bronchiolar expression of NF-E2-related factor 2-regulated antioxidant and detoxification genes, heme oxygenase-1, reduced nicotinamide adenine dinucleotide phosphate quinone reductase 1, and glutamate-cysteine ligase, modifier unit, or antioxidant activity in bronchoalveolar lavage fluid, regardless of CS exposure. In summary, aging increases susceptibility to CS-induced inflammation in a mouse model, and robust mRNA up-regulation and nuclear translocation of NF-kappaB in bronchiolar epithelium may be involved.
authors.affiliation: First Department of Medicine, Hokkaido University School of Medicine, N-15, W-7, Kita-ku, Sapporo, Japan.
authors.forename: Chinatsu
authors.initials: C
authors.lastname: Moriyama
authors.forename: Tomoko
authors.initials: T
authors.lastname: Betsuyaku
authors.forename: Yoko
authors.initials: Y
authors.lastname: Ito
authors.forename: Ichiro
authors.initials: I
authors.lastname: Hamamura
authors.forename: Junko
authors.initials: J
authors.lastname: Hata
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Takahashi
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Nasuhara
authors.forename: Masaharu
authors.initials: M
authors.lastname: Nishimura
mesh_terms: D000375:Aging / Q000473:pathology*; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D055745:Bronchioles / Q000201:enzymology / Q000473:pathology*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D018925:Chemokines / Q000235:genetics / Q000378:metabolism*; D002633:Chemotaxis; D004198:Disease Susceptibility; D004848:Epithelium / Q000378:metabolism / Q000473:pathology; D005786:Gene Expression Regulation; D007150:Immunohistochemistry; D007249:Inflammation / Q000139:chemically induced* / Q000473:pathology*; D007700:Kinetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000378:metabolism; D009504:Neutrophils / Q000166:cytology / Q000378:metabolism; D009195:Peroxidase / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012907:Smoking / Q000009:adverse effects*
chemical_list: D000975:Antioxidants; D018925:Chemokines; D016328:NF-kappa B; D012333:RNA, Messenger; D009195:Peroxidase