Disruption of Nrf2 enhances susceptibility to airway inflammatory responses induced by low-dose diesel exhaust particles in mice
Abstract
To test our hypothesis that diesel exhaust particle (DEP)-induced oxidative stress and host antioxidant responses play a key role in the development of DEP-induced airway inflammatory diseases, C57BL/6 nuclear erythroid 2 P45-related factor 2 (Nrf2) knockout (Nrf2(-/-)) and wild-type mice were exposed to low-dose DEP for 7 h/day, 5 days/week, for 8 weeks. Nrf2(-/-) mice exposed to low-dose DEP showed significantly increased airway hyperresponsiveness and counts of lymphocytes and eosinophils, together with increased concentrations of IL-12 and IL-13, and thymus and activation-regulated chemokine (TARC), in BAL fluid than wild-type mice. In contrast, expression of antioxidant enzyme genes was significantly higher in wild-type mice than in Nrf2(-/-) mice. We have first demonstrated that disruption of Nrf2 enhances susceptibility to airway inflammatory responses induced by inhalation of low-dose DEP in mice. These results strongly suggest that DEP-induced oxidative stress and host antioxidant responses play some role in the development of DEP-induced airway inflammation.
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Disruption of Nrf2 enhances susceptibility to allergic airway inflammatory responses induced by chronic exposure to diesel exhaust PM.
“Additionally, disruption of Nrf2 has been shown to enhance susceptibility to allergic airway inflammatory responses induced by chronic exposure to diesel exhaust PM [146].”
From Air pollution and children’s health—a review of adverse effects associated with prenatal exposure from fine to ultrafine particulate matter (2021) · cites this paper as [146]
Cites
Disruption of <i>Nrf2</i> enhances susceptibility to severe airway inflammation and asthma in mice
Rangasamy, T., Guo, J., Mitzner, W. A., Roman, J., Singh, A., Fryer, A. D., Yamamoto, M., Kensler, T. W., Tuder, R. M., Georas, S. N., et al. (2005) · The Journal of Experimental Medicine · doi:10.1084/jem.20050538 · Cited by 580 · see citing works
Self-citationXiao, G. G., Wang, M., Li, N., Loo, J. A., & Nel, A. E. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m306423200 · Cited by 428 · see citing works
Kawasaki, S., Takizawa, H., Yoneyama, H., Nakayama, T., Fujisawa, R., Izumizaki, M., Imai, T., Yoshie, O., Homma, I., Yamamoto, K., et al. (2001) · The Journal of Immunology · doi:10.4049/jimmunol.166.3.2055 · Cited by 261 · see citing works
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Johnson, N. M., Hoffmann, A. R., Behlen, J. C., Lau, C., Pendleton, D., Harvey, N., Shore, R., Li, Y., Chen, J., Tian, Y., et al. (2021) · Environmental Health and Preventive Medicine · doi:10.1186/s12199-021-00995-5 · Cited by 339 · see citing works
“Additionally, disruption of Nrf2 has been shown to enhance susceptibility to allergic airway inflammatory responses induced by chronic exposure to diesel exhaust PM [146].”
BackgroundSelf-citationIn utero ultrafine particulate matter exposure causes offspring pulmonary immunosuppression
Rychlik, K. A., Secrest, J. R., Lau, C., Pulczinski, J., Zamora, M. L., Leal, J., Langley, R., Myatt, L. G., Raju, M., Chang, R. C.-A., et al. (2019) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1816103116 · Cited by 98 · see citing works
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- Authors
- Li, Y. J., Takizawa, H., Azuma, A., Kohyama, T., Yamauchi, Y., Takahashi, S., Yamamoto, M., Kawada, T., Kudoh, S., & Sugawara, I.
- Affiliations
- Nippon Medical School (JP)
- Teikyo University (JP)
- The University of Tokyo (JP)
- University of Tsukuba (JP)
- Corresponding author
- Sugawara, Isamu
- ORCID
- Venue
- Clinical Immunology
- Publisher
- Elsevier BV
- Published
- 2008-09
- Volume
- 128
- Issue
- 3
- Pages
- 366-373
- ISSN
- 1521-6616 (ISSN-L)
- OpenAlex
- W2090449144
- Cited by
- 70
- References
- 3
- Citations by year
- 2025: 1 · 2024: 2 · 2021: 4 · 2020: 3 · 2019: 4 · 2018: 2 · 2017: 3 · 2016: 3 · 2015: 7 · 2014: 7 · 2013: 9 · 2012: 5
- FWCI
- 4.51
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Clinical Immunology (publishedVersion)
- PubMed (publishedVersion)
- Institutional Repositories DataBase (IRDB) (submittedVersion)
- Topics
- Health Sciences › Medicine › Physiology › Asthma and respiratory diseases
- Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Air Quality and Health Impacts
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics, phytochemicals, and oxidative stress
- Keywords
- Nrf2, diesel exhaust particles, airway inflammation, oxidative stress, antioxidant response, airway hyperresponsiveness, eosinophils, IL-12, IL-13, CCL17, Nrf2 knockout mice, particulate matter inhalation
- MeSH terms
- Animals, Antioxidants, Vehicle Emissions, Bronchoalveolar Lavage Fluid, Disease Susceptibility, Enzyme Induction, Immunoglobulin E, Immunoglobulin G, Inflammation, Lung, Mice, Inbred C57BL, Respiratory System, Cytokines, Bronchial Hyperreactivity, Mice, Knockout, Oxidative Stress, Inhalation Exposure, NF-E2-Related Factor 2, Mice
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