Imperial College London
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ProfessorFrankKelly

Faculty of Medicine, School of Public Health

Battcock Chair in Community Health and Policy
 
 
 
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Contact

 

+44 (0)20 7594 8098 ext 48098frank.kelly Website

 
 
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Location

 

Sir Michael Uren HubWhite City Campus

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Summary

 

Publications

Citation

BibTex format

@article{Friberg:2023:10.1186/s12989-023-00559-1,
author = {Friberg, M and Behndig, AF and Bosson, JA and Muala, A and Barath, S and Dove, R and Glencross, D and Kelly, FJ and Blomberg, A and Mudway, IS and Sandström, T and Pourazar, J},
doi = {10.1186/s12989-023-00559-1},
journal = {Particle and Fibre Toxicology},
title = {Human exposure to diesel exhaust induces CYP1A1 expression and AhR activation without a coordinated antioxidant response},
url = {http://dx.doi.org/10.1186/s12989-023-00559-1},
volume = {20},
year = {2023}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - BACKGROUND: Diesel exhaust (DE) induces neutrophilia and lymphocytosis in experimentally exposed humans. These responses occur in parallel to nuclear migration of NF-κB and c-Jun, activation of mitogen activated protein kinases and increased production of inflammatory mediators. There remains uncertainty regarding the impact of DE on endogenous antioxidant and xenobiotic defences, mediated by nuclear factor erythroid 2-related factor 2 (Nrf2) and the aryl hydrocarbon receptor (AhR) respectively, and the extent to which cellular antioxidant adaptations protect against the adverse effects of DE. METHODS: Using immunohistochemistry we investigated the nuclear localization of Nrf2 and AhR in the epithelium of endobronchial mucosal biopsies from healthy subjects six-hours post exposure to DE (PM10, 300 µg/m3) versus post-filtered air in a randomized double blind study, as a marker of activation. Cytoplasmic expression of cytochrome P450s, family 1, subfamily A, polypeptide 1 (CYP1A1) and subfamily B, Polypeptide 1 (CYP1B1) were examined to confirm AhR activation; with the expression of aldo-keto reductases (AKR1A1, AKR1C1 and AKR1C3), epoxide hydrolase and NAD(P)H dehydrogenase quinone 1 (NQO1) also quantified. Inflammatory and oxidative stress markers were examined to contextualize the responses observed. RESULTS: DE exposure caused an influx of neutrophils to the bronchial airway surface (p = 0.013), as well as increased bronchial submucosal neutrophil (p < 0.001), lymphocyte (p = 0.007) and mast cell (p = 0.002) numbers. In addition, DE exposure enhanced the nuclear translocation of the AhR and increased the CYP1A1 expression in the bronchial epithelium (p = 0.001 and p = 0.028, respectively). Nuclear translocation of AhR was also increased in the submucosal leukocytes (p < 0.001). Epithelial nuclear AhR expression was negatively associated with bro
AU  - Friberg,M
AU  - Behndig,AF
AU  - Bosson,JA
AU  - Muala,A
AU  - Barath,S
AU  - Dove,R
AU  - Glencross,D
AU  - Kelly,FJ
AU  - Blomberg,A
AU  - Mudway,IS
AU  - Sandström,T
AU  - Pourazar,J
DO  - 10.1186/s12989-023-00559-1
PY  - 2023///
SN  - 1743-8977
TI  - Human exposure to diesel exhaust induces CYP1A1 expression and AhR activation without a coordinated antioxidant response
T2  - Particle and Fibre Toxicology
UR  - http://dx.doi.org/10.1186/s12989-023-00559-1
UR  - https://www.ncbi.nlm.nih.gov/pubmed/38062420
UR  - http://hdl.handle.net/10044/1/109956
VL  - 20
ER  -
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