NRF2 targeting: a promising therapeutic strategy in chronic obstructive pulmonary disease

Boutten, Anne; Goven, Delphine; Artaud-Macari, Élise; Boczkowski, Jorge; Bonay, Marcel

doi:10.1016/j.molmed.2011.02.006

Cited by 198 publications

(159 citation statements)

References 78 publications

(151 reference statements)

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“…A number of researchers have proposed that Nrf2 activation should be a central goal in the prevention and management of COPD, and have presented evidence that Nrf2 can protect oxidant-stressed lungs in a range of complementary ways [57,58]. Nrf2 supports efficient proteasomal activity by inducing certain proteasomal subunits; this in turn can mitigate cigarette smoke-induced endoplasmic reticulum stress and subsequent apoptosis [59].…”

Section: Adjuvant Strategies Targeting Nrf2mentioning

confidence: 99%

DHA May Have a Profoundly Protective Impact on the Lungs of Smokers

Mf¹

2016

J Nutr Food Sci

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Evidence has accumulated over the last twenty years that smokers who frequently ingest fish are at lower risk for both chronic obstructive pulmonary disease (COPD) and lung cancer. Plasma phospholipid levels of DHA, but not EPA, have been reported to correlate inversely with risk for COPD in smokers, suggesting that DHA may be primarily responsible for the apparent protection afforded to lungs of smokers by fish consumption. Meanwhile, evidence is emerging that certain metabolites of DHA -including 4 -hydroxy hexenal (4-HHE), 17 -oxo -DHA, and resolvin D1 -can activate Nrf2 -mediated transcription of heme oxygenase -1 and other antioxidant / cytoprotective enzymes. Since the oxidant stress imposed by cigarette smoke exposure could be expected to promote peroxidation of membrane DHA and hence boost production of 4 -HHE, DHA in lung membranes may in effect up-regulate the protective feedback mechanism whereby oxidative stress provokes Nrf2 -mediated induction of cytoprotective enzymes. DHA can also give rise to the autacoid resolvin D1, which, via activation of a receptor, suppresses NFkappaB activation and the consequent production of pro-inflammatory cytokines. Resolvin D1 can also inhibit macrophage NADPH oxidase and promote an anti-inflammatory M2 phenotype in lung macrophages. Not surprisingly, inhalation of resolvin D1 has a marked anti-inflammatory impact on the lungs of mice exposed to tobacco smoke. These considerations help to rationalize the epidemiology linking fish consumption to lung health, and suggest that smokers who can't or won't quit their habit would be well advised to consume fish or DHA supplements regularly. Higher intakes of fruits and vegetables -likely in part because many of these contain Nrf2 -activating phytochemicals -likewise are associated with lower risk for COPD, and can be recommended for smokers.Keywords: COPD; Lung cancer; Fish; Docosahexaenoic acid (DHA); 4 -hydroxy hexenal; Nrf2; Resolvin D1 Fish Consumption May Protect Smokers from COPDLimited but nonetheless compelling epidemiology has linked heavy dietary consumption of fresh fish to marked decreases in risk for lung cancer and chronic obstructive pulmonary disease (COPD) among smokers. The first key evidence in this regard emerged in 1994. Shahar et al.[1] studied subjects enrolled in the prospective Atherosclerosis Risk in Communities (ARIC) study, who had received a dietary assessment and a physical exam including lung spirometry, and had been questioned regarding lung symptoms [1]. COPD was defined by three separate criteria: self -reported symptoms of chronic bronchitis, physician diagnosis of emphysema, and via spirometry (FEV1 < 65% of predicted value). When risk for COPD was compared between the first and fourth quartiles of estimated daily intake of eicosapentaenoic acid (EPA) plus docosahexaenoic acid (DHA), relative risk for COPD in the fourth quartile (mean omega-3 intake 480 mg) after appropriate multivariate adjustments was found to be 0.66 (95% CI 0.52 -0.85), 0.31 (CI 0.18 -0.52), and 0.50 (CI 0.32...

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Section: Adjuvant Strategies Targeting Nrf2mentioning

confidence: 99%

DHA May Have a Profoundly Protective Impact on the Lungs of Smokers

Mf¹

2016

J Nutr Food Sci

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“…Au cours des cancers, le rôle de Nrf2 est actuellement incertain [31]. Différents arguments suggèrent que les gènes induits par Nrf2 ont un rôle protecteur vis-à-vis du cancer [32] et que le défaut de Nrf2 contribue à une susceptibilité accrue des patients atteints de BPCO post-tabagique au développement d'un cancer pulmonaire [33]. Ainsi, les gènes codant pour des antioxydants sont diminués dans l'épithélium pulmonaire de patients fumeurs atteints de cancer [34].…”

Section: Keap1unclassified

“…Récemment une mutation de Keap1 à l'origine d'une augmentation de l'expression de Nrf2 a été détectée dans des lignées de cancer du poumon, et est impliquée dans la résistance aux chimiothérapies [33]. De même, une mutation de Nrf2 s'accompagnant d'un défaut de son élimi-nation par le protéasome a été identifiée chez 10 % des patients atteints de cancer du poumon et est associée au processus de cancérisation [37].…”

Section: Nrf2unclassified

La voie Nrf2 en pathologie respiratoire

et al. 2011

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“…More importantly, Nrf2 deficiency influences susceptibility to steroid resistance (Adenuga et al, 2010;Malhotra et al, 2011), and can improve antibacterial defenses and prevent exacerbations of COPD caused by bacterial infection (Harvey et al, 2011), so Nrf2 is considered to be a promising therapeutic target in COPD (Boutten et al, 2011). However, another study showed that the expression of Nrf2 decreased in COPD patients (Suzuki et al, 2008), but nuclear factorkappa B (NF-κB), a transcription factor involved in the regulation of inflammatory cytokines such as interleukin-8 (IL-8), increased in the airway epithelial cells of COPD patients and patients who smoked, especially in patients with acute exacerbations of COPD (Maziak et al, 1998;Corradi et al, 1999;Rahman et al, 2002;Block and Hong, 2005).…”

Section: Introductionmentioning

confidence: 99%

15-Deoxy-prostaglandin J2 anti-inflammation in a rat model of chronic obstructive pulmonary disease and human bronchial epithelial cells via Nrf2 activation

Luo

Wang

et al. 2015

Genet. Mol. Res.

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ABSTRACT. Nuclear factor-erythroid 2-related factor 2 (Nrf2) is a transcription factor that regulates antioxidant and anti-inflammatory genes, and it plays a crucial role in the pathogenesis of chronic obstructive pulmonary disease (COPD). Moreover, 15-deoxy-delta12,14-prostaglandin J2 (15d-PGJ2) plays a protective role against oxidative stress and inflammation both in vivo and in vitro. In a previous study, we found that 15d-PGJ2 increased the expression of Nrf2 in a COPD rat model. This study aims to elucidate the role of 15d-PGJ2 in COPD pathogenesis and the relationship between Nrf2 and human bronchial epithelial (HBE) cells. Normal HBE (HBE) cells were cultured. Following cigarette smoke extract (CSE) stimulation, pre-incubation with or without small interfering RNA (siRNA) Nrf2, and stimulation with or without 15d-PGJ2, the expression levels of Nrf2, NF-κBp65, and IL-8 were detected by reverse transcriptionpolymerase chain reaction and western blot, respectively. The expression of NF-κBp65 and IL-8 in CSE-stimulated normal HBE cells was inhibited by 15d-PGJ2 at both the mRNA level and the protein level. Moreover, the expression of Nrf2 in normal HBE cells was improved by 15d-PGJ2 at both the mRNA level and the protein level. However, the inhibitory or improving effects of 15d-PGJ2 were disengaged by siRNA Nrf2 at both the mRNA level and the protein level. 15d-PGJ2 possesses anti-inflammatory properties in the pathogenesis of COPD, and HBE cells stimulated by CSE via Nrf2 activation.

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NRF2 targeting: a promising therapeutic strategy in chronic obstructive pulmonary disease

Cited by 198 publications

References 78 publications

DHA May Have a Profoundly Protective Impact on the Lungs of Smokers

DHA May Have a Profoundly Protective Impact on the Lungs of Smokers

La voie Nrf2 en pathologie respiratoire

15-Deoxy-prostaglandin J2 anti-inflammation in a rat model of chronic obstructive pulmonary disease and human bronchial epithelial cells via Nrf2 activation

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