The DOI matches its Crossref record; 40 of the 40 references it cites were found in a registry or an index.
Diesel exhaust particles induce oxidative stress, proinflammatory signaling, and P‐glycoprotein up‐regulation at the blood‐brain barrier
Open accessAbstract
Here, we report that diesel exhaust particles (DEPs), a major constituent of urban air pollution, affect blood‐brain barrier function at the tissue, cellular, and molecular levels. Isolated rat brain capillaries exposed to DEPs showed increased expression and transport activity of the key drug efflux transporter, P‐glycoprotein (6 h EC 50 was ~5 μg/ml). Upregulation of P‐glycoprotein was abolished by blocking transcription or protein synthesis. Inhibition of NADPH oxidase or pretreatment of capillaries with radical scavengers ameliorated DEP‐induced P‐glycoprotein up‐regulation, indicating a role for reactive oxygen species in signaling. DEP exposure also increased brain capillary tumor necrosis factor‐α (TNF‐α) levels. DEP‐induced P‐glycoprotein up‐regulation was abolished when TNF‐receptor 1 (TNF‐R1) was blocked and was not evident in experiments with capillaries from TNF‐R1 knockout mice. Inhibition of JNK, but not NF‐κB, blocked DEP‐induced P‐glycoprotein up‐regulation, indicating a role for AP‐1 in the signaling pathway. Consistent with this, DEPs increased phosphorylation of c‐jun. Together, our results show for the first time that a component of air pollution, DEPs, alters blood‐brain barrier function through oxidative stress and proinflammatory cytokine production. These experiments disclose a novel blood‐brain barrier signaling pathway, with clear implications for environmental toxicology, CNS pathology, and the pharmacotherapy of CNS disorders.—Hartz, A. M. S., Bauer, B., Block, M. L., Hong, J.‐S., Miller, D.‐S. Diesel exhaust particles induce oxidative stress, proinflammatory signaling, and P‐glycoprotein up‐regulation at the blood‐brain barrier. FASEB J. 22, 2723–2733 (2008)
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Cites
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Cited by
Brook, R. D., Rajagopalan, S., Pope, C. A., Brook, J. R., Bhatnagar, A., Diez-Roux, A. V., Holguin, F., Hong, Y., Luepker, R. V., Mittleman, M. A., et al. (2010) · Circulation · doi:10.1161/cir.0b013e3181dbece1 · Cited by 6,548
de Bont, J., Jaganathan, S., Dahlquist, M., Persson, Å., Stafoggia, M., & Ljungman, P. (2022) · Journal of Internal Medicine · doi:10.1111/joim.13467 · Cited by 574
The outdoor air pollution and brain health workshop
Block, M. L., Elder, A., Auten, R. L., Bilbo, S. D., Chen, H., Chen, J.-C., Cory-Slechta, D. A., Costa, D., Diaz-Sanchez, D., Dorman, D. C., et al. (2012) · NeuroToxicology · doi:10.1016/j.neuro.2012.08.014 · Cited by 539
Self-citationMaternal lifestyle and environmental risk factors for autism spectrum disorders
Lyall, K., Schmidt, R. J., & Hertz-Picciotto, I. (2014) · International Journal of Epidemiology · doi:10.1093/ije/dyt282 · Cited by 427
Levesque, S., Taetzsch, T., Lull, M. E., Kodavanti, U., Stadler, K., Wagner, A., Johnson, J. A., Duke, L., Kodavanti, P., Surace, M. J., et al. (2011) · Environmental Health Perspectives · doi:10.1289/ehp.1002986 · Cited by 371
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Metadata
- Authors
- Hartz, A. M. S., Bauer, B., Block, M. L., Hong, J.-S., & Miller, D. S.
- Venue
- The FASEB Journal
- Publisher
- Wiley
- Published
- 2008-05-12
- Volume
- 22
- Issue
- 8
- Pages
- 2723-2733
- ISSN
- 0892-6638 (ISSN-L)
- 1530-6860
- OpenAlex
- W1974572321
- Cited by
- 268
- References
- 40
- FWCI
- 7.87
- Type
- journal article
- Language
- en
- Open access
- green
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