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

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

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::ca0eb9d507eee41b2d4c0c5fe194b631Test
https://www.mdpi.com/2073-4409/9/5/1123Test

المؤلفون: Seo-Hyeon Choi, Ji-Eun Kim, Min-Jeong Kong, Tae-Cheon Kang, Hana Park

المصدر: Cells
Volume 8
Issue 7
Cells, Vol 8, Iss 7, p 746 (2019)

مصطلحات موضوعية: 0301 basic medicine, Male, CCR2, animal diseases, p38 mitogen-activated protein kinases, seizure, LAMP1, p38 Mitogen-Activated Protein Kinases, Monocytes, Article, Rats, Sprague-Dawley, 03 medical and health sciences, 0302 clinical medicine, Status Epilepticus, medicine, Roscovitine, Animals, Protein kinase A, lcsh:QH301-705.5, CD68, Neuroinflammation, Chemokine CCL2, Microglia, Iba-1, Chemistry, Kinase, Cyclin-dependent kinase 5, Monocyte, Lysosome-Associated Membrane Glycoproteins, General Medicine, biochemical phenomena, metabolism, and nutrition, Cell biology, Frontal Lobe, Rats, SB202190, 030104 developmental biology, medicine.anatomical_structure, lcsh:Biology (General), nervous system, Blood-Brain Barrier, IB4, epilepsy, 030217 neurology & neurosurgery, NFκB

الوصف: Under physiological conditions, microglia are unique immune cells resident in the brain that is isolated from the systemic immune system by brain-blood barrier. Following status epilepticus (SE, a prolonged seizure activity), microglia are rapidly activated and blood-derived monocytes that infiltrate the brain
therefore, the regulations of microglia activation and monocyte infiltration are one of the primary therapeutic strategies for inhibition of undesirable consequences from SE. Roscovitine, a potent (but not selective) cyclin-dependent kinase 5 (CDK5) inhibitor, has been found to exert anti-inflammatory and microglia-inhibiting actions in several in vivo models, although the underlying mechanisms have not been clarified. In the present study, roscovitine attenuated SE-induces monocyte infiltration without vasogenic edema formation in the frontoparietal cortex (FPC), accompanied by reducing expressions of monocyte chemotactic protein-1 (MCP-1) and lysosome-associated membrane protein 1 (LAMP1) in resident microglia, while it did not affect microglia transformation to amoeboid form. Furthermore, roscovitine ameliorated the up-regulation of p38 mitogen-activated protein kinase (p38 MAPK) phosphorylation, but not nuclear factor-κB-S276 phosphorylation. Similar to roscovitine, SB202190, a p38 MAPK inhibitor, mitigated monocyte infiltration and microglial expressions of MCP-1 and LAMP1 in the FPC following SE. Therefore, these findings suggest for the first time that roscovitine may inhibit SE-induced neuroinflammation via regulating p38 MAPK-mediated microglial responses.

وصف الملف: application/pdf

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::5572531333ed44bd3639f683be60d90fTest
https://pubmed.ncbi.nlm.nih.gov/31331032Test