Altered vulnerability to asthma at various levels of ambient Benzo[a]Pyrene by CTLA4, STAT4 and CYP2E1 polymorphisms

Choi, Hye‐Seon; Tabashidze, Nana; Rössner, Pavel; Dostál, Miroslav; Pastorková, Anna; Kong, Sek Won; Gmuender, Hans; Šrám, Radìm J.

doi:10.1016/j.envpol.2017.07.057

Cited by 26 publications

(21 citation statements)

References 53 publications

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“…In our investigation, we could not directly examine whether non-atopic asthma represents T-helper 2 or type 2 low asthma, while atopic asthma captures Thelper 2 or type 2 high asthma, two known endotypes [3,30]. This is because we did not measure typical [9,10,13,19,[31][32][33][34][35][36]. Both the laboratory and epidemiologic evidence have shown that PAHs could induce or enhance allergic sensitization, exacerbate pre-existing asthma, and enhance the risk of de novo asthma development [33,37,38].…”

Section: Discussionmentioning

confidence: 96%

“…For example, the interquartile range of ambient B[a]P levels during our exposure window of interest (i.e. November, 2008) is representative of the ambient concentrations from the earlier years [12].…”

Section: Discussionmentioning

confidence: 99%

“…The study population's socioeconomic traits, exposure sources, and overall approaches are described [10,12,13]. Brie y, a case-control study was conducted on 191 asthmatic and 194 control children on November 2008.…”

Section: Methodsmentioning

confidence: 99%

“…Publicly available ambient concentration of benzo[a]pyrene is downloaded from the Czech Hydrometeorological Institute [17]. Eight particle-bound PAHs are routinely monitored using Versatile Air Pollution Sampler [18][19][20].…”

Section: Air Pollution Monitoring Of Polycyclic Aromatic Hydrocarbonsmentioning

confidence: 99%

“…cigarette smoke and other anthropogenic compounds) have been shown to predict de novo asthma development during childhood [8]. Our group too has documented signi cant associations among neighborhood level of polyaromatic hydrocarbon (PAH), speci cally, benzo[a]pyrene (B[a]P), multiple putative biomarkers, and clinically diagnosed asthma in children [9][10][11][12][13][14][15]. Furthermore, our analysis suggest for the rst time that childhood B[a]P exposure predicts dose-responsive, integrative -Omics based mechanisms of asthma, mediated by dysregulated hematopoiesis among the asthma cases, compared to the controls [11].…”

Section: Introductionmentioning

confidence: 99%

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Benzo[a]pyrene-associated Oxidative Stress is Divergent in Non-atopic Versus Atopic Children, and Suggest They May Represent Asthma Endotypes: A Case-control Study

Choi

Dostál²,

Pastorková³

et al. 2020

Preprint

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Background For nearly 50% of the asthmatic children, effective treatments against exacerbation do not exist, because existing therapies do not target the mechanistic origins of discrete sub-diseases (i.e. endotypes). While non-atopic and atopic asthma represent known phenotypes, it is unknown whether they arise from disparate processes. The objective is to classify two phenotypes (non-atopic vs. atopic asthma) into endotypes using polyaromatic hydrocarbon, namely, benzo[a]pyrene, as putative marker of endotype. Methods In a case-control study, lean controls (i.e. reference) are compared against three outcomes of interest – overweight/obese controls, lean asthmatics (without overweight/obesity), and overweight/obese asthmatics – in terms of benzo[a]pyrene exposure level, plasma 15-Ft2-isoprostane, urinary 8-oxo-7,8-dihydro-2’-deoxyguanosine, as well as their history of co-morbidities until age three, following atopy- and gender-stratification. Results The non-atopic girls are associated with significantly elevated median benzo[a]pyrene for the lean asthmatics (11.2 ng/m3) and the overweight/obese asthmatics (18.0 ng/m3), compared to the non-atopic control girls (4.3 ng/m3; p-value < 0.001). A natural-log (ln) unit increase B[a]P exposure predicts 10-times greater odds of asthma in the lean non-atopic boys, while the same exposure is not associated with asthma among the lean atopic boys. The diagnosis of lung function deficit, which only appear among those with highest median value of B[a]P, appears to be a particularly important predictor of non-atopic asthma only. The non-atopic asthmatic boys with highest exposure to B[a]P (median, 20 ng/m3) were also positively diagnosis with lung function deficit, compared to the non-atopic controls (median, 4.3 ng/m3). An elevated exposure to B[a]P is associated with depressed systemic oxidant levels, and correspondingly elevated odds of non-atopic asthma. On the other hand, low ambient exposure to B[a]P, and weakly pro-inflammatory effect of oxidative stress of such exposure, is not associated with atopic asthma. Conclusions Ambient benzo[a]pyrene is robustly associated with non-atopic asthma, while it has no clear associations with atopic asthma among the lean children. Our observation, once validated in a prospective cohort design, could aid the development of targeted and personalized therapies in children in whom the respiratory injuries are still reversible.

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Section: Discussionmentioning

confidence: 96%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Air Pollution Monitoring Of Polycyclic Aromatic Hydrocarbonsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Benzo[a]pyrene-associated Oxidative Stress is Divergent in Non-atopic Versus Atopic Children, and Suggest They May Represent Asthma Endotypes: A Case-control Study

Choi

Dostál²,

Pastorková³

et al. 2020

Preprint

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Wogonin alleviates BaP‐induced DNA damage and oxidative stress in human airway epithelial cells by dual inhibiting CYP1A1 activity and expression

et al. 2023

Environmental Toxicology

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Benzo[a]pyrene (BaP) is a common air pollutant that has been reported to cause oxidative stress and carcinogenesis. Wogonin, a flavonoid compound extracted from the roots of Scutellaria baicalensis, has been found to possess a variety of pharmacological activities, including anti‐inflammatory and anti‐cancer effects. The purpose of this study was to examine the ability of wogonin to alleviate the cytotoxicity induced by BaP in human airway epithelial cells and explore the corresponding mechanism. Our study found that wogonin treatment inhibited DNA damage and reactive oxygen species overproduction induced by BaP in human airway epithelial cells. In vitro enzyme assays showed that wogonin significantly inhibited the enzymatic activity of CYP1A1. In addition, wogonin decreased the basal level of CYP1A1 and inhibited the CYP1A1 overexpression induced by BaP, whereas overexpression of CYP1A1 partially reversed the effect of wogonin on BaP‐induced DNA damage. Meanwhile, a CYP1A1 inhibitor and CYP1A1 knockdown also showed these same effects. Further studies showed that wogonin regulates CYP1A1 expression by inhibiting CDK7 and CDK9 activity. The use of CDK7 or CDK9 inhibitors decreased BaP‐induced cytotoxicity and CYP1A1 expression. Finally, we found that the methoxy group of wogonin was crucial for its inhibitory activity. In conclusion, our data indicated that wogonin could effectively relieve BaP induced cytotoxicity, and its mechanism was related to the dual inhibition of CYP1A1 activity and expression.

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Interactions between environmental pollutants and genetic susceptibility in asthma risk

Johansson

Mersha

Brandt

et al. 2019

Current Opinion in Immunology

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Altered vulnerability to asthma at various levels of ambient Benzo[a]Pyrene by CTLA4, STAT4 and CYP2E1 polymorphisms

Cited by 26 publications

References 53 publications

Benzo[a]pyrene-associated Oxidative Stress is Divergent in Non-atopic Versus Atopic Children, and Suggest They May Represent Asthma Endotypes: A Case-control Study

Benzo[a]pyrene-associated Oxidative Stress is Divergent in Non-atopic Versus Atopic Children, and Suggest They May Represent Asthma Endotypes: A Case-control Study

Wogonin alleviates BaP‐induced DNA damage and oxidative stress in human airway epithelial cells by dual inhibiting CYP1A1 activity and expression

Interactions between environmental pollutants and genetic susceptibility in asthma risk

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