Aging enhances susceptibility to cigarette smoke-induced inflammation through bronchiolar chemokines

Chinatsu Moriyama, Tomoko Betsuyaku, Yoko Ito, Ichiro Hamamura, Junko Hata, Hiroshi Takahashi, Yasuyuki Nasuhara, Masaharu Nishimura

Research output: Contribution to journalArticlepeer-review

26 Citations (Scopus)

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 amousemodel 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-weekold mice showed a greater number of neutrophils and higher levels of bronchiolar KCand 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-κB. 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-κB in bronchiolar epithelium may be involved.

Original languageEnglish
Pages (from-to)304-311
Number of pages8
JournalAmerican journal of respiratory cell and molecular biology
Volume42
Issue number3
DOIs
Publication statusPublished - 2010 Mar 1

Keywords

  • Age
  • Bronchiolar epithelium
  • Chemokine
  • Neutrophil
  • Smoking

ASJC Scopus subject areas

  • Molecular Biology
  • Pulmonary and Respiratory Medicine
  • Clinical Biochemistry
  • Cell Biology

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