Cited by 130Genomics, phytochemicals, and oxidative stressAsthma and respiratory diseasesRedox biology and oxidative stress

Role of the Nrf2-Mediated Signaling Pathway as a Negative Regulator of Inflammation: Implications for the Impact of Particulate Pollutants on Asthma

Li, Ning, Nel, Andre E.·2006·Antioxidants & Redox Signaling

Abstract

Particulate matter (PM) is an environmental factor that may contribute to the exacerbation and possibly the development of asthma. PM contain redox-active chemicals and transition metals which generate reactive oxygen species (ROS). Excessive ROS can induce oxidative stress, which proceeds in hierarchical fashion to generate cellular responses. The most sensitive cellular response to mild oxidative stress is the activation of antioxidant and phase II enzymes (tier 1). If this protection fails, further increase of oxidative stress can induce inflammation (tier 2) and cell death (tier 3). Tier 1 antioxidant defenses are critical for protecting against airway inflammation and asthma. The expression of these antioxidant enzymes is regulated by the transcription factor, Nrf2. In response to oxidative stress, Nrf2 escapes from Keap1-mediated proteasomal degradation resulting in prolonged protein half-life and its nuclear accumulation. Nrf2 interacts with the antioxidant response element (ARE) in the promoters of phase II enzyme genes, leading to their transcriptional activation. Several phase II expression polymorphisms are associated with an increased risk of asthma. The indispensable role of Nrf2 in tier-1 oxidative stress response suggests that polymorphisms of Nrf2-regulated genes may be useful susceptibility markers for asthma. Moreover, chemopreventive Nrf2 inducers may be used for treating PM-exacerbated asthma.

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Crossref · 10.1089/ars.2006.8.88

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Authors
Li, N., & Nel, A. E.
Affiliations
  • University of California, Los Angeles (US)
  • Division of Clinical Immunology and Allergy, Department of Medicine, University of California, Los Angeles, California.
Venue
Antioxidants & Redox Signaling
Published
2006-01
Volume
8
Issue
1-2
Pages
88-98
ISSN
  • 1523-0864 (ISSN-L)
  • 1557-7716
OpenAlex
W1991248184
Cited by
130
References
117
Citations by year
2026: 1 · 2025: 2 · 2024: 3 · 2022: 2 · 2021: 7 · 2020: 6 · 2019: 6 · 2018: 3 · 2017: 6 · 2016: 8 · 2015: 8 · 2014: 8 · 2013: 9 · 2012: 6
FWCI
1.06
Type
journal article
Language
en
Open access
closed
Locations
  • Antioxidants and Redox Signaling (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics, phytochemicals, and oxidative stress
  • Health Sciences › Medicine › Physiology › Asthma and respiratory diseases
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
Keywords
Nrf2 signaling, particulate matter, asthma, air pollution, oxidative stress, reactive oxygen species, Keap1, antioxidant response element, phase II enzymes, antioxidant enzymes, airway inflammation, genetic polymorphism, asthma susceptibility, chemoprevention, Nrf2 inducers
MeSH terms
Animals, Asthma, Environmental Pollutants, Humans, Inflammation, Signal Transduction, Reactive Oxygen Species, Oxidative Stress, NF-E2-Related Factor 2

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