Microglia NLRP3 Inflammasomes Activation Involving Diabetic Neuroinflammation in Diabetic Mice and BV2 Cells.
BV2 cells.
Diabetes
MAPKs
NF-κB
NLPR3
ROS
Journal
Current pharmaceutical design
ISSN: 1873-4286
Titre abrégé: Curr Pharm Des
Pays: United Arab Emirates
ID NLM: 9602487
Informations de publication
Date de publication:
Historique:
received:
05
11
2020
accepted:
27
02
2021
pubmed:
20
7
2021
medline:
1
6
2022
entrez:
19
7
2021
Statut:
ppublish
Résumé
Hyperglycemia-induced microglia activation can cause a continuous release of proinflammatory cytokines, which gradually damages neurons and contributes to central diabetic neuroinflammation. This study aimed to illustrate the possible mechanism related to NLRP3 inflammasome and the aggravation of diabetes neuroinflammation. The targeted proteins from BV2 cells and brain tissues were tested by Western blot or immunohistochemistry. Cytokines from cell supernatant and serum were detected by ELISA. Meanwhile, cytoplasm and mitochondria ROS were determined by DCFHDA and Mito sox Red, respectively. In vitro, BV2 cells were stimulated by different glucose concentrations (5.5 to 65 mM/L) above physiological values and maintained for different periods (12 to 48h). The proinflammatory cytokines IL-1β, IL18, IL6, TNFα and cytoplasm ROS were significantly increased in a dose-dependent manner, while mitochondrial ROS was unaffected. NLRP3 inflammasomes, MAPKs, and NF-κB pathways were obviously activated at the concentration of 35 mM/L for 12h. Inhibition assay using specific inhibitors indicated that the treatment of glucose (35 mM/L for 12h) could stimulate NLRP3 inflammasome activation via ROS/JNK MAPKs/NF-κB pathway. In STZ induced diabetes mice models, microglia NLRP3, ASC, and caspase-1 proteins were highly expressed, and serum cytokines IL-1β, IL6, IL18, and TNFα were remarkably increased. Microglia NLRP3 inflammasomes activation involves diabetic neuroinflammation in diabetic mice and BV2 cells via ROS/JNK MAPKs/NF-κB pathways.
Sections du résumé
BACKGROUND
BACKGROUND
Hyperglycemia-induced microglia activation can cause a continuous release of proinflammatory cytokines, which gradually damages neurons and contributes to central diabetic neuroinflammation.
OBJECTIVE
OBJECTIVE
This study aimed to illustrate the possible mechanism related to NLRP3 inflammasome and the aggravation of diabetes neuroinflammation.
METHODS
METHODS
The targeted proteins from BV2 cells and brain tissues were tested by Western blot or immunohistochemistry. Cytokines from cell supernatant and serum were detected by ELISA. Meanwhile, cytoplasm and mitochondria ROS were determined by DCFHDA and Mito sox Red, respectively.
RESULTS
RESULTS
In vitro, BV2 cells were stimulated by different glucose concentrations (5.5 to 65 mM/L) above physiological values and maintained for different periods (12 to 48h). The proinflammatory cytokines IL-1β, IL18, IL6, TNFα and cytoplasm ROS were significantly increased in a dose-dependent manner, while mitochondrial ROS was unaffected. NLRP3 inflammasomes, MAPKs, and NF-κB pathways were obviously activated at the concentration of 35 mM/L for 12h. Inhibition assay using specific inhibitors indicated that the treatment of glucose (35 mM/L for 12h) could stimulate NLRP3 inflammasome activation via ROS/JNK MAPKs/NF-κB pathway. In STZ induced diabetes mice models, microglia NLRP3, ASC, and caspase-1 proteins were highly expressed, and serum cytokines IL-1β, IL6, IL18, and TNFα were remarkably increased.
CONCLUSION
CONCLUSIONS
Microglia NLRP3 inflammasomes activation involves diabetic neuroinflammation in diabetic mice and BV2 cells via ROS/JNK MAPKs/NF-κB pathways.
Identifiants
pubmed: 34279193
pii: CPD-EPUB-116742
doi: 10.2174/1381612827666210716104606
doi:
Substances chimiques
Inflammasomes
0
NF-kappa B
0
NLR Family, Pyrin Domain-Containing 3 Protein
0
Nlrp3 protein, mouse
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
2802-2816Subventions
Organisme : Project of Science and Technology Department of Jilin Province
ID : 20180414036GH
Organisme : Education Department of Jilin Province
ID : 2016444
Organisme : State’s Key Project of Research and Development Plan
ID : 2017YFD0502200, 2016YFD0501302
Organisme : National Natural Science Foundation of China
ID : 31172364, 81801972
Organisme : Fund for Science and Technology Development of Jilin Province
ID : 20150101108JC
Organisme : Important National Science and Technology Specific Projects
ID : 2012ZX10003002
Organisme : Program for New Century Excellent Talents in University
ID : NCET-09-0434
Organisme : Science, Technology and Innovation Commission of Shenzhen Municipality
ID : JCYJ2016031100720906, JSGG20160301100442775
Informations de copyright
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