VX765 Attenuates Pyroptosis and HMGB1/TLR4/NF-
Journal
Oxidative medicine and cellular longevity
ISSN: 1942-0994
Titre abrégé: Oxid Med Cell Longev
Pays: United States
ID NLM: 101479826
Informations de publication
Date de publication:
2020
2020
Historique:
received:
10
08
2019
revised:
28
02
2020
accepted:
20
03
2020
entrez:
8
5
2020
pubmed:
8
5
2020
medline:
5
2
2021
Statut:
epublish
Résumé
Traumatic brain injury (TBI) refers to temporary or permanent damage to brain function caused by penetrating objects or blunt force trauma. TBI activates inflammasome-mediated pathways and other cell death pathways to remove inactive and damaged cells, however, they are also harmful to the central nervous system. The newly discovered cell death pattern termed pyroptosis has become an area of interest. It mainly relies on caspase-1-mediated pathways, leading to cell death. Our research focus is VX765, a known caspase-1 inhibitor which may offer neuroprotection after the process of TBI. We established a controlled cortical impact (CCI) mouse model and then controlled the degree of pyroptosis in TBI with VX765. The effects of caspase-1 inhibition on inflammatory response, pyroptosis, blood-brain barrier (BBB), apoptosis, and microglia activation, in addition to neurological deficits, were investigated. We found that TBI led to NOD-like receptors (NLRs) as well as absent in melanoma 2 (AIM2) inflammasome-mediated pyroptosis in the damaged cerebral cortex. VX765 curbed the expressions of indispensable inflammatory subunits (caspase-1 as well as key downstream proinflammatory cytokines such as interleukin- (IL-) 1 In conclusion, VX765 can counteract neurological damage after TBI by reducing pyroptosis and HMGB1/TLR4/NF-
Sections du résumé
BACKGROUND
BACKGROUND
Traumatic brain injury (TBI) refers to temporary or permanent damage to brain function caused by penetrating objects or blunt force trauma. TBI activates inflammasome-mediated pathways and other cell death pathways to remove inactive and damaged cells, however, they are also harmful to the central nervous system. The newly discovered cell death pattern termed pyroptosis has become an area of interest. It mainly relies on caspase-1-mediated pathways, leading to cell death.
METHODS
METHODS
Our research focus is VX765, a known caspase-1 inhibitor which may offer neuroprotection after the process of TBI. We established a controlled cortical impact (CCI) mouse model and then controlled the degree of pyroptosis in TBI with VX765. The effects of caspase-1 inhibition on inflammatory response, pyroptosis, blood-brain barrier (BBB), apoptosis, and microglia activation, in addition to neurological deficits, were investigated.
RESULTS
RESULTS
We found that TBI led to NOD-like receptors (NLRs) as well as absent in melanoma 2 (AIM2) inflammasome-mediated pyroptosis in the damaged cerebral cortex. VX765 curbed the expressions of indispensable inflammatory subunits (caspase-1 as well as key downstream proinflammatory cytokines such as interleukin- (IL-) 1
CONCLUSION
CONCLUSIONS
In conclusion, VX765 can counteract neurological damage after TBI by reducing pyroptosis and HMGB1/TLR4/NF-
Identifiants
pubmed: 32377306
doi: 10.1155/2020/7879629
pmc: PMC7181015
doi:
Substances chimiques
Dipeptides
0
HMGB1 Protein
0
NF-kappa B
0
TLR4 protein, human
0
Toll-Like Receptor 4
0
para-Aminobenzoates
0
belnacasan
00OLE78529
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
7879629Informations de copyright
Copyright © 2020 Zhezhe Sun et al.
Déclaration de conflit d'intérêts
No competing financial interests exist.
Références
Nat Rev Neurol. 2017 Sep;13(9):572
pubmed: 28776601
Metab Brain Dis. 2017 Oct;32(5):1395-1402
pubmed: 28303450
Front Immunol. 2016 Dec 05;7:556
pubmed: 27994591
Trends Neurosci. 2017 Jan;40(1):39-59
pubmed: 27939821
J Cereb Blood Flow Metab. 2017 Aug;37(8):2952-2962
pubmed: 27864465
Cell Res. 2015 Dec;25(12):1285-98
pubmed: 26611636
Innate Immun. 2014 Feb;20(2):115-25
pubmed: 23676582
Neurochem Res. 2017 Nov;42(11):3296-3309
pubmed: 28786047
Nature. 2015 Oct 29;526(7575):666-71
pubmed: 26375259
Molecules. 2019 Jan 21;24(2):
pubmed: 30669620
Brain Res. 2015 Oct 5;1622:230-9
pubmed: 26080076
Int J Neuropsychopharmacol. 2015 Jan 20;18(8):
pubmed: 25603858
Neuroreport. 2018 Jul 4;29(10):794-803
pubmed: 29683870
Bio Protoc. 2017 May 20;7(10):
pubmed: 29085861
J Biol Chem. 2010 Feb 26;285(9):6477-88
pubmed: 20038581
Immunol Rev. 2017 May;277(1):61-75
pubmed: 28462526
Metab Brain Dis. 2017 Aug;32(4):1133-1145
pubmed: 28401330
Brain Res. 2006 Sep 13;1109(1):14-21
pubmed: 16857176
J Neuroinflammation. 2018 Feb 19;15(1):48
pubmed: 29458437
Mediators Inflamm. 2013;2013:124614
pubmed: 23864765
J Neuroinflammation. 2015 Jul 30;12:137
pubmed: 26224068
J Biol Chem. 2010 Mar 26;285(13):9792-802
pubmed: 20093358
Cell Death Discov. 2017 Nov 13;3:17070
pubmed: 29147575
Int J Biochem Cell Biol. 2018 Jun;99:64-71
pubmed: 29597004
Psychopharmacology (Berl). 2019 Jul;236(7):2173-2185
pubmed: 30847567
RNA Biol. 2015;12(7):681-9
pubmed: 26016563
Neurobiol Dis. 2018 Sep;117:15-27
pubmed: 29859317
J Neuroinflammation. 2019 Feb 8;16(1):27
pubmed: 30736791
Biochim Biophys Acta Mol Basis Dis. 2018 Jan;1864(1):226-237
pubmed: 29066283
Oncogene. 2006 Oct 30;25(51):6831-43
pubmed: 17072331
J Pineal Res. 2017 Aug;63(1):
pubmed: 28398673
J Neurotrauma. 2016 Oct 1;33(19):1732-1750
pubmed: 26486881
J Neurotrauma. 2007 Oct;24(10):1545-57
pubmed: 17970618
Nature. 2016 Jul 06;535(7610):153-8
pubmed: 27383986
Front Neurol. 2013 Mar 04;4:18
pubmed: 23459929
Respir Res. 2018 Nov 22;19(1):230
pubmed: 30466433
Pharmacol Ther. 2018 Jul;187:133-149
pubmed: 29466702
Neurosurgery. 2002 Jul;51(1):195-203; discussion 203
pubmed: 12182417
Cell Death Differ. 2007 Sep;14(9):1590-604
pubmed: 17599095
Proc Natl Acad Sci U S A. 2018 Jun 26;115(26):E6065-E6074
pubmed: 29895691
Acta Pharmacol Sin. 2017 Nov;38(11):1445-1455
pubmed: 28770828
J Neuroinflammation. 2014 Apr 24;11:82
pubmed: 24761998
Science. 2016 Aug 19;353(6301):783-5
pubmed: 27540166
Neurochem Res. 2016 Feb;41(1-2):193-209
pubmed: 26555554
Mol Med Rep. 2017 Oct;16(4):3922-3928
pubmed: 29067455
J Cereb Blood Flow Metab. 2013 Dec;33(12):1864-74
pubmed: 23942366
Trends Biochem Sci. 2017 Apr;42(4):245-254
pubmed: 27932073
Trends Immunol. 2017 Apr;38(4):261-271
pubmed: 28196749
Clin Exp Rheumatol. 2016 Jan-Feb;34(1):111-8
pubmed: 26742834
Front Immunol. 2016 Sep 22;7:378
pubmed: 27713747
Neurosci Lett. 2011 Jul 8;498(2):147-52
pubmed: 21596098
Med Hypotheses. 2013 Sep;81(3):484-6
pubmed: 23831306
J Chin Med Assoc. 2019 Jun;82(6):452-456
pubmed: 30932940
Lancet Neurol. 2013 Jan;12(1):53-64
pubmed: 23177532
Cell Physiol Biochem. 2017;43(2):481-491
pubmed: 28934735
Sci Rep. 2014 Oct 24;4:6718
pubmed: 25342226
Nature. 2011 Oct 16;479(7371):117-21
pubmed: 22002608
Nature. 2015 Oct 29;526(7575):660-5
pubmed: 26375003
J Neuroinflammation. 2017 Aug 23;14(1):167
pubmed: 28835272
FASEB J. 2015 Sep;29(9):3863-75
pubmed: 26045547
Nature. 2016 Jul 7;535(7610):111-6
pubmed: 27281216
Arch Med Res. 2014 Nov;45(8):698-710
pubmed: 25446615
Front Neurosci. 2018 Sep 11;12:628
pubmed: 30271319
Spine (Phila Pa 1976). 2013 Dec 15;38(26):E1641-8
pubmed: 24335635
J Cell Physiol. 2018 Jul;233(7):5160-5169
pubmed: 29150951
J Leukoc Biol. 2019 Apr;105(4):783-795
pubmed: 30776150
J Cereb Blood Flow Metab. 2014 Apr;34(4):621-9
pubmed: 24398937
Int J Mol Med. 2016 Apr;37(4):921-30
pubmed: 26936125
J Pharm Pharmacol. 2020 Apr;72(4):539-550
pubmed: 32034779
Mol Neurobiol. 2015 Apr;51(2):766-78
pubmed: 24939693
J Neurotrauma. 2018 Jul 15;35(14):1681-1693
pubmed: 29439605
Mol Neurobiol. 2016 Dec;53(10):7298-7311
pubmed: 26687235