CDDO-Me Inhibits Microglial Activation and Monocyte Infiltration by Abrogating NFκB- and p38 MAPK-Mediated Signaling Pathways Following Status Epilepticus
| العنوان: | CDDO-Me Inhibits Microglial Activation and Monocyte Infiltration by Abrogating NFκB- and p38 MAPK-Mediated Signaling Pathways Following Status Epilepticus |
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| المؤلفون: | Ji-Eun Kim, Tae-Cheon Kang, Hana Park, Ji-Eun Lee |
| المصدر: | Cells, Vol 9, Iss 1123, p 1123 (2020) Cells Volume 9 Issue 5 |
| بيانات النشر: | MDPI AG, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | Male, MAP Kinase Signaling System, NF-E2-Related Factor 2, p38 mitogen-activated protein kinases, seizure, SN50, Models, Biological, p38 Mitogen-Activated Protein Kinases, Monocytes, Article, Nrf2, Rats, Sprague-Dawley, Phosphoserine, Status Epilepticus, Parietal Lobe, medicine, Animals, Oleanolic Acid, Phosphorylation, Protein kinase A, CD68, lcsh:QH301-705.5, Chemokine CCL2, Neuroinflammation, Microglia, Iba-1, Tumor Necrosis Factor-alpha, Chemistry, Monocyte, NF-kappa B, General Medicine, Frontal Lobe, medicine.anatomical_structure, lcsh:Biology (General), IB4, Cancer research, epilepsy, Tumor necrosis factor alpha, Signal transduction, Peptides |
| الوصف: | Following status epilepticus (SE, a prolonged seizure activity), microglial activation, and monocyte infiltration result in the inflammatory responses in the brain that is involved in the epileptogenesis. Therefore, the regulation of microglia/monocyte-mediated neuroinflammation is one of the therapeutic strategies for avoidance of secondary brain injury induced by SE. 2-cyano-3,12-dioxooleana-1,9-dien-28-oic acid methyl ester (CDDO-Me RTA 402) is an activator of nuclear factor-erythroid 2-related factor 2 (Nrf2), which regulates intracellular redox homeostasis. In addition, CDDO-Me has anti-inflammatory properties that suppress microglial proliferation and its activation, although the underlying mechanisms have not been clarified. In the present study, CDDO-Me ameliorated monocyte infiltration without vasogenic edema formation in the frontoparietal cortex (FPC) following SE, accompanied by abrogating monocyte chemotactic protein-1 (MCP-1)/tumor necrosis factor-&alpha (TNF-&alpha ) expressions and p38 mitogen-activated protein kinase (p38 MAPK) phosphorylation. Furthermore, CDDO-Me inhibited nuclear factor-&kappa B (NF&kappa B)-S276 phosphorylation and microglial transformation, independent of Nrf2 expression. Similar to CDDO-Me, SN50 (an NF&kappa B inhibitor) mitigated monocyte infiltration by reducing MCP-1 and p38 MAPK phosphorylation in the FPC following SE. Therefore, these findings suggest, for the first time, that CDDO-Me may attenuate microglia/monocyte-mediated neuroinflammation via modulating NF&kappa B- and p38 MAPK-MCP-1 signaling pathways following SE. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 2073-4409 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::ca0eb9d507eee41b2d4c0c5fe194b631Test https://www.mdpi.com/2073-4409/9/5/1123Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....ca0eb9d507eee41b2d4c0c5fe194b631 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 20734409 |
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