Cited by 286Genomics, phytochemicals, and oxidative stressChronic Obstructive Pulmonary Disease (COPD) ResearchHeme Oxygenase-1 and Carbon Monoxide

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·2008·American Journal of Respiratory Cell and Molecular Biology

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.

Integrity signals

Registry

Crossref · 10.1165/rcmb.2007-0424oc

Cites

38 of 38 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Experimental studies have illustrated an age-associated increase in ROS levels that corresponds with decreased antioxidative responses in AM.

    “Experimental studies have illustrated an age-associated increase in ROS levels that corresponds with decreased antioxidative responses in AM (111, 112).”

    From Aging and Lung Disease (2020) · cites this paper as [112]

Cites

Flagged first, then by citations

Cited by

Sorted by citations

Authors
Suzuki, M., Betsuyaku, T., Ito, Y., Nagai, K., Nasuhara, Y., Kaga, K., Kondo, S., & Nishimura, M.
Affiliations
  • Hokkaido University (JP)
  • First Department of Medicine and
Venue
American Journal of Respiratory Cell and Molecular Biology
Published
2008-12-01
Volume
39
Issue
6
Pages
673-682
ISSN
  • 1044-1549 (ISSN-L)
  • 1535-4989
OpenAlex
W2095835362
Cited by
286
References
38
Citations by year
2026: 7 · 2025: 6 · 2024: 13 · 2023: 11 · 2022: 14 · 2021: 20 · 2020: 23 · 2019: 14 · 2018: 11 · 2017: 18 · 2016: 22 · 2015: 12 · 2014: 17 · 2013: 23 · 2012: 17
FWCI
7.81
Type
journal article
Language
en
Open access
closed
Locations
  • American Journal of Respiratory Cell and Molecular Biology (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics, phytochemicals, and oxidative stress
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Chronic Obstructive Pulmonary Disease (COPD) Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Heme Oxygenase-1 and Carbon Monoxide
Keywords
Nrf2, lung macrophages, alveolar macrophages, chronic obstructive pulmonary disease, cigarette smoke, aging, Nrf2 target genes, glutathione disulfide, oxidative stress, antioxidant defense, emphysema
MeSH terms
Adult, Aged, Aging, Animals, Bronchoalveolar Lavage Fluid, Female, Humans, Immunohistochemistry, Lung, Male, Mice, Inbred C57BL, Mice, Inbred ICR, Middle Aged, RNA, Messenger, Smoking, Biomarkers, Down-Regulation, Macrophages, Alveolar, Oxidative Stress, Pulmonary Disease, Chronic Obstructive, NF-E2-Related Factor 2, Mice

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review