The DOI matches its Crossref record; 9 of the 9 references it cites were found in a registry or an index.
PPARα ligands inhibit radiation-induced microglial inflammatory responses by negatively regulating NF-κB and AP-1 pathways
Open accessAbstract
Whole-brain irradiation (WBI) can lead to cognitive impairment several months to years after irradiation. Studies on rodents have shown a rapid and sustained increase in activated microglia (brain macrophages) following brain irradiation, contributing to a chronic inflammatory response and a corresponding decrease in hippocampal neurogenesis. Thus, alleviating microglial activation following radiation represents a key strategy to minimize WBI-induced morbidity. We hypothesized that pre-treatment with peroxisomal proliferator-activated receptor (PPAR)α agonists would ameliorate the pro-inflammatory responses seen in the microglia following in vitro radiation. Irradiating BV-2 cells (a murine microglial cell line) with single doses (2-10 Gy) of 137Cs γ-rays led to increases in 1] the gene expression of IL-1β and TNFα, 2] Cox-2 protein levels and 3] intracellular ROS generation. In addition, an increase in the DNA-binding activity of redox-regulated pro-inflammatory transcription factors AP-1 and NF-κB was observed. Pre-treating BV-2 cells with the PPARα agonists, GW7647 and Fenofibrate significantly inhibited the radiation-induced microglial pro-inflammatory response, in part, via decreasing i] the nuclear translocation of the NF-κB p65 subunit and ii] phosphorylation of the c-jun subunit of AP-1 in the nucleus. Taken together, these data support the hypothesis that activation of PPARα can modulate the radiation-induced microglial pro-inflammatory response.
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Cites
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Cited by
Stewart, F. A., Akleyev, A. V., Hauer-Jensen, M., Hendry, J. H., Kleiman, N. J., MacVittie, T. J., Aleman, B. M., Edgar, A. B., Mabuchi, K., Muirhead, C. R., et al. (2012) · Annals of the ICRP · doi:10.1016/j.icrp.2012.02.001 · Cited by 1,604
Molecular Actions of PPARα in Lipid Metabolism and Inflammation
Bougarne, N., Weyers, B., Desmet, S. J., Deckers, J., Ray, D. W., Staels, B., & De Bosscher, K. (2018) · Endocrine Reviews · doi:10.1210/er.2018-00064 · Cited by 898
Self-regulation of the inflammatory response by peroxisome proliferator-activated receptors
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PPARα: Energy Combustion, Hypolipidemia, Inflammation and Cancer
Pyper, S. R., Viswakarma, N., Yu, S., & Reddy, J. K. (2010) · Nuclear Receptor Signaling · doi:10.1621/nrs.08002 · Cited by 379
Qiu, Y.-Y., Zhang, J., Zeng, F.-Y., & Zhu, Y. Z. (2023) · Pharmacological Research · doi:10.1016/j.phrs.2023.106786 · Cited by 271
Metadata
- Authors
- Ramanan, S., Kooshki, M., Zhao, W., Hsu, F.-C., & Robbins, M. E.
- Venue
- Free Radical Biology and Medicine
- Publisher
- Elsevier BV
- Published
- 2008-12
- Volume
- 45
- Issue
- 12
- Pages
- 1695-1704
- ISSN
- 0891-5849 (ISSN-L)
- OpenAlex
- W2085116908
- Cited by
- 159
- References
- 9
- FWCI
- 4.12
- Type
- journal article
- Language
- en
- Open access
- green
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- Ramanan, S., Kooshki, M., Zhao, W., Hsu, F.-C., & Robbins, M. E. (2008). PPARα ligands inhibit radiation-induced microglial inflammatory responses by negatively regulating NF-κB and AP-1 pathways. Free Radical Biology and Medicine. https://doi.org/10.1016/j.freeradbiomed.2008.09.002
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