Abstract
Pulmonary macrophages are one of the sources of various antioxidant and detoxification enzymes for which NF-E2-related factor 2 (Nrf2) is a key transcriptional factor. Although Nrf2 deficiency reportedly induces severe emphysema in mice exposed to cigarette smoke (CS), no reports have studied Nrf2 regulation in chronic obstructive pulmonary disease (COPD). In this study, Nrf2 activation in response to CS was evaluated in human alveolar macrophages, and age-related differences in CS-induced Nrf2 regulation in mouse alveolar macrophages were determined. Furthermore, Nrf2 mRNA levels in human macrophages harvested by bronchoalveolar lavage or laser capture microdissection were measured. CS induced nuclear Nrf2 accumulation and up-regulation of Nrf2 target genes without substantial changes in Nrf2 mRNA levels in human alveolar macrophages. In humans, the Nrf2 mRNA level in lavaged macrophages of young subjects (n = 14) was independent of smoking status; however, the Nrf2 mRNA level was down-regulated in the lavaged macrophages of older current smokers (n = 14) compared with older nonsmokers (n = 9) (P < 0.001). Among older subjects, the macrophage Nrf2 mRNA level was inversely correlated with oxidized glutathione and carbonylated albumin levels in bronchoalveolar lavage fluid. In mice, aging suppressed the CS-induced up-regulation of Nrf2 target genes, as well as Nrf2, in alveolar macrophages. Furthermore, the Nrf2 mRNA level was decreased in laser capture microdissection-retrieved macrophages obtained from subjects with COPD (n = 10) compared with control subjects (n = 10) (P = 0.001). In conclusion, CS induces Nrf2 activation in macrophages, and Nrf2 expression is decreased in the macrophages of older current smokers and patients with COPD.
| Original language | English |
|---|---|
| Pages (from-to) | 673-682 |
| Number of pages | 10 |
| Journal | American Journal of Respiratory Cell and Molecular Biology |
| Volume | 39 |
| Issue number | 6 |
| DOIs | |
| Publication status | Published - 2008 Dec 1 |
| Externally published | Yes |
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Keywords
- Bronchoalveolar lavage
- Cigarette smoking
- Laser capture microdissection
ASJC Scopus subject areas
- Cell Biology
- Pulmonary and Respiratory Medicine
- Molecular Biology
- Clinical Biochemistry
Cite this
Down-regulated NF-E2-related factor 2 in pulmonary macrophages of aged smokers and patients with chronic obstructive pulmonary disease. / Suzuki, Masaru; Betsuyaku, Tomoko; Ito, Yoko; Nagai, Katsura; Nasuhara, Yasuyuki; Kaga, Kichizo; Kondo, Satoshi; Nishimura, Masaharu.
In: American Journal of Respiratory Cell and Molecular Biology, Vol. 39, No. 6, 01.12.2008, p. 673-682.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Down-regulated NF-E2-related factor 2 in pulmonary macrophages of aged smokers and patients with chronic obstructive pulmonary disease
AU - Suzuki, Masaru
AU - Betsuyaku, Tomoko
AU - Ito, Yoko
AU - Nagai, Katsura
AU - Nasuhara, Yasuyuki
AU - Kaga, Kichizo
AU - Kondo, Satoshi
AU - Nishimura, Masaharu
PY - 2008/12/1
Y1 - 2008/12/1
N2 - Pulmonary macrophages are one of the sources of various antioxidant and detoxification enzymes for which NF-E2-related factor 2 (Nrf2) is a key transcriptional factor. Although Nrf2 deficiency reportedly induces severe emphysema in mice exposed to cigarette smoke (CS), no reports have studied Nrf2 regulation in chronic obstructive pulmonary disease (COPD). In this study, Nrf2 activation in response to CS was evaluated in human alveolar macrophages, and age-related differences in CS-induced Nrf2 regulation in mouse alveolar macrophages were determined. Furthermore, Nrf2 mRNA levels in human macrophages harvested by bronchoalveolar lavage or laser capture microdissection were measured. CS induced nuclear Nrf2 accumulation and up-regulation of Nrf2 target genes without substantial changes in Nrf2 mRNA levels in human alveolar macrophages. In humans, the Nrf2 mRNA level in lavaged macrophages of young subjects (n = 14) was independent of smoking status; however, the Nrf2 mRNA level was down-regulated in the lavaged macrophages of older current smokers (n = 14) compared with older nonsmokers (n = 9) (P < 0.001). Among older subjects, the macrophage Nrf2 mRNA level was inversely correlated with oxidized glutathione and carbonylated albumin levels in bronchoalveolar lavage fluid. In mice, aging suppressed the CS-induced up-regulation of Nrf2 target genes, as well as Nrf2, in alveolar macrophages. Furthermore, the Nrf2 mRNA level was decreased in laser capture microdissection-retrieved macrophages obtained from subjects with COPD (n = 10) compared with control subjects (n = 10) (P = 0.001). In conclusion, CS induces Nrf2 activation in macrophages, and Nrf2 expression is decreased in the macrophages of older current smokers and patients with COPD.
AB - Pulmonary macrophages are one of the sources of various antioxidant and detoxification enzymes for which NF-E2-related factor 2 (Nrf2) is a key transcriptional factor. Although Nrf2 deficiency reportedly induces severe emphysema in mice exposed to cigarette smoke (CS), no reports have studied Nrf2 regulation in chronic obstructive pulmonary disease (COPD). In this study, Nrf2 activation in response to CS was evaluated in human alveolar macrophages, and age-related differences in CS-induced Nrf2 regulation in mouse alveolar macrophages were determined. Furthermore, Nrf2 mRNA levels in human macrophages harvested by bronchoalveolar lavage or laser capture microdissection were measured. CS induced nuclear Nrf2 accumulation and up-regulation of Nrf2 target genes without substantial changes in Nrf2 mRNA levels in human alveolar macrophages. In humans, the Nrf2 mRNA level in lavaged macrophages of young subjects (n = 14) was independent of smoking status; however, the Nrf2 mRNA level was down-regulated in the lavaged macrophages of older current smokers (n = 14) compared with older nonsmokers (n = 9) (P < 0.001). Among older subjects, the macrophage Nrf2 mRNA level was inversely correlated with oxidized glutathione and carbonylated albumin levels in bronchoalveolar lavage fluid. In mice, aging suppressed the CS-induced up-regulation of Nrf2 target genes, as well as Nrf2, in alveolar macrophages. Furthermore, the Nrf2 mRNA level was decreased in laser capture microdissection-retrieved macrophages obtained from subjects with COPD (n = 10) compared with control subjects (n = 10) (P = 0.001). In conclusion, CS induces Nrf2 activation in macrophages, and Nrf2 expression is decreased in the macrophages of older current smokers and patients with COPD.
KW - Bronchoalveolar lavage
KW - Cigarette smoking
KW - Laser capture microdissection
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UR - http://www.scopus.com/inward/citedby.url?scp=57349151482&partnerID=8YFLogxK
U2 - 10.1165/rcmb.2007-0424OC
DO - 10.1165/rcmb.2007-0424OC
M3 - Article
C2 - 18566336
AN - SCOPUS:57349151482
VL - 39
SP - 673
EP - 682
JO - American Journal of Respiratory Cell and Molecular Biology
JF - American Journal of Respiratory Cell and Molecular Biology
SN - 1044-1549
IS - 6
ER -