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Citation
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HERO ID
156694
Reference Type
Journal Article
Subtype
Review
Title
Role of the Nrf2-mediated signaling pathway as a negative regulator of inflammation: Implications for the impact of particulate pollutants on asthma
Author(s)
Li, N; Nel, AE
Year
2006
Is Peer Reviewed?
Yes
Journal
Antioxidants & Redox Signaling
ISSN:
1523-0864
EISSN:
1557-7716
Volume
8
Issue
1-2
Page Numbers
88-98
Language
English
PMID
16487041
DOI
10.1089/ars.2006.8.88
Web of Science Id
WOS:000236964000008
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.
Tags
•
ISA-PM (2009 Final Project Page)
2009 Final
•
ISA-PM (2019)
Peer Input Draft
Chapter 5
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