Microglia Depletion Attenuates the Pro-Resolving Activity of the Formyl Peptide Receptor 2 Agonist AMS21 Related to Inhibition of Inflammasome NLRP3 Signalling Pathway: A Study of Organotypic Hippocampal Cultures.
formyl peptide receptor 2
hippocampus
inflammasome NLPR3-related pathway
lipopolysaccharide
neuroinflammation
ureidopropanamide agonist
Journal
Cells
ISSN: 2073-4409
Titre abrégé: Cells
Pays: Switzerland
ID NLM: 101600052
Informations de publication
Date de publication:
03 Nov 2023
03 Nov 2023
Historique:
received:
20
09
2023
revised:
16
10
2023
accepted:
31
10
2023
medline:
13
11
2023
pubmed:
10
11
2023
entrez:
10
11
2023
Statut:
epublish
Résumé
Microglial cells have been demonstrated to be significant resident immune cells that maintain homeostasis under physiological conditions. However, prolonged or excessive microglial activation leads to disturbances in the resolution of inflammation (RoI). Formyl peptide receptor 2 (FPR2) is a crucial player in the RoI, interacting with various ligands to induce distinct conformational changes and, consequently, diverse biological effects. Due to the poor pharmacokinetic properties of endogenous FPR2 ligands, the aim of our study was to evaluate the pro-resolving effects of a new ureidopropanamide agonist, compound AMS21, in hippocampal organotypic cultures (OHCs) stimulated with lipopolysaccharide (LPS). Moreover, to assess whether AMS21 exerts its action via FPR2 specifically located on microglial cells, we conducted a set of experiments in OHCs depleted of microglial cells using clodronate. We demonstrated that the protective and anti-inflammatory activity of AMS21 manifested as decreased levels of lactate dehydrogenase (LDH), nitric oxide (NO), and proinflammatory cytokines IL-1β and IL-6 release evoked by LPS in OHCs. Moreover, in LPS-stimulated OHCs, AMS21 treatment downregulated NLRP3 inflammasome-related factors (CASP1, NLRP3, PYCARD) and this effect was mediated through FPR2 because it was blocked by the FPR2 antagonist WRW4 pre-treatment. Importantly this beneficial effect of AMS21 was only observed in the presence of microglial FPR2, and absent in OHCs depleted with microglial cells using clodronate. Our results strongly suggest that the compound AMS21 exerts, at nanomolar doses, protective and anti-inflammatory properties and an FPR2 receptor located specifically on microglial cells mediates the anti-inflammatory response of AMS21. Therefore, microglial FPR2 represents a promising target for the enhancement of RoI.
Identifiants
pubmed: 37947648
pii: cells12212570
doi: 10.3390/cells12212570
pmc: PMC10648897
pii:
doi:
Substances chimiques
Inflammasomes
0
NLR Family, Pyrin Domain-Containing 3 Protein
0
Receptors, Formyl Peptide
0
Lipopolysaccharides
0
Clodronic Acid
0813BZ6866
Anti-Inflammatory Agents
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : CANALETTO Polish National Agency for Academic Exchange, Poland
ID : PPN/BIT/2021/1/00009/U/00001
Organisme : HARMONIA National Science Centre, Poland
ID : 2017/26/M/NZ7/01048
Références
Biotechniques. 1993 Sep;15(3):532-4, 536-7
pubmed: 7692896
Nat Neurosci. 2015 Nov;18(11):1584-93
pubmed: 26436904
Nat Immunol. 2008 Aug;9(8):857-65
pubmed: 18604209
Pharmacol Rev. 2009 Jun;61(2):119-61
pubmed: 19498085
J Neuroimmunol. 2013 Jan 15;254(1-2):10-8
pubmed: 22999806
Curr Drug Targets CNS Neurol Disord. 2005 Aug;4(4):435-52
pubmed: 16101559
J Immunol. 2007 Sep 15;179(6):4142-52
pubmed: 17785853
Int J Mol Sci. 2013 Apr 02;14(4):7193-230
pubmed: 23549262
FEBS J. 2022 Apr;289(7):1801-1822
pubmed: 33811735
Trends Pharmacol Sci. 2022 Aug;43(8):669-685
pubmed: 35031144
Neuroscience. 2009 Feb 6;158(3):1030-8
pubmed: 18644426
Front Cell Neurosci. 2019 Feb 04;13:19
pubmed: 30778288
Neuroscientist. 2003 Feb;9(1):10-22
pubmed: 12580336
J Pharmacol Exp Ther. 1996 May;277(2):1097-102
pubmed: 8627521
J Neuroinflammation. 2017 Dec 20;14(1):256
pubmed: 29262843
Mol Neurobiol. 2019 Aug;56(8):5365-5380
pubmed: 30610610
Nat Commun. 2015 Oct 28;6:8761
pubmed: 26508369
Int J Mol Sci. 2021 Feb 04;22(4):
pubmed: 33557113
Science. 2011 Sep 9;333(6048):1456-8
pubmed: 21778362
Int J Med Sci. 2020 Jul 19;17(13):1936-1945
pubmed: 32788872
Br J Pharmacol. 2009 Oct;158(4):947-59
pubmed: 19785661
Front Aging Neurosci. 2022 May 19;14:827263
pubmed: 35663580
Eur J Pharm Sci. 1999 May;8(2):109-18
pubmed: 10210733
Int J Mol Sci. 2013 May 08;14(5):9820-33
pubmed: 23698769
Trends Pharmacol Sci. 2015 Nov;36(11):737-755
pubmed: 26478210
ACS Chem Neurosci. 2020 Nov 18;11(22):3707-3731
pubmed: 33146995
Mol Neurobiol. 2021 Dec;58(12):6203-6221
pubmed: 34468933
Nat Neurosci. 2021 Mar;24(3):343-354
pubmed: 33558694
Cell Biosci. 2019 Mar 27;9:31
pubmed: 30962873
Semin Immunopathol. 2019 Nov;41(6):699-709
pubmed: 31705317
J Neuroinflammation. 2019 Mar 28;16(1):66
pubmed: 30922332
J Neuroinflammation. 2020 Aug 14;17(1):239
pubmed: 32795323
Nature. 2013 Jan 31;493(7434):674-8
pubmed: 23254930
Neurochem Res. 2018 Aug;43(8):1587-1598
pubmed: 29948727
Front Pharmacol. 2023 Feb 09;14:1125982
pubmed: 36969855
Proc Natl Acad Sci U S A. 2010 Jan 26;107(4):1660-5
pubmed: 20080636
Nature. 2021 Nov;599(7883):102-107
pubmed: 34616039
Trends Mol Med. 2019 Nov;25(11):967-979
pubmed: 31597593
J Neurochem. 2010 May;113(3):749-60
pubmed: 20141570
Brain Behav Immun. 2017 Aug;64:367-383
pubmed: 28263786
ACS Pharmacol Transl Sci. 2020 Jan 20;3(1):88-106
pubmed: 32259091
J Neuroinflammation. 2012 May 31;9:116
pubmed: 22651847
Front Pharmacol. 2015 Nov 05;6:262
pubmed: 26594174
J Neurosci Methods. 1991 Apr;37(2):173-82
pubmed: 1715499
PLoS One. 2015 Jun 19;10(6):e0130624
pubmed: 26091541
Cell Mol Immunol. 2021 Sep;18(9):2114-2127
pubmed: 34321623
Glia. 2011 Feb;59(2):242-55
pubmed: 21125645
J Affect Disord. 2023 Aug 15;335:358-370
pubmed: 37217098
Cells. 2021 Jun 17;10(6):
pubmed: 34204273
J Leukoc Biol. 2021 Mar;109(3):561-571
pubmed: 32531835
Br J Pharmacol. 2022 Oct;179(19):4617-4639
pubmed: 35797341
Int J Neurosci. 2017 Jul;127(7):624-633
pubmed: 27412492
ChemMedChem. 2017 Nov 22;12(22):1839-1847
pubmed: 28922577
Curr Neuropharmacol. 2016;14(2):155-64
pubmed: 26639457
Pharmacol Rep. 2021 Aug;73(4):1004-1019
pubmed: 34105114
Front Neurol. 2020 Sep 18;11:570711
pubmed: 33071950
Eur J Med Chem. 2021 Mar 5;213:113167
pubmed: 33486199
PLoS One. 2014 Mar 06;9(6):e90613
pubmed: 24603667
J Neuroinflammation. 2021 Nov 6;18(1):258
pubmed: 34742308
Cells. 2020 Jul 12;9(7):
pubmed: 32664639
Pharmacol Rep. 2019 Aug;71(4):603-613
pubmed: 31176102
Cells. 2021 Sep 09;10(9):
pubmed: 34572022
Int J Mol Sci. 2018 Jul 05;19(7):
pubmed: 29976873
Neuron. 2022 Nov 2;110(21):3458-3483
pubmed: 36327895
Front Cell Neurosci. 2015 Mar 12;9:82
pubmed: 25814933
Int Immunopharmacol. 2022 Sep;110:109070
pubmed: 35978514
Trends Immunol. 2016 Sep;37(9):608-620
pubmed: 27443914
Molecules. 2021 Feb 11;26(4):
pubmed: 33670164
Nat Protoc. 2006;1(5):2452-6
pubmed: 17406491
Neurochem Res. 2010 Dec;35(12):2018-26
pubmed: 21042851
Neural Regen Res. 2019 Dec;14(12):2071-2072
pubmed: 31397336
Curr Neuropharmacol. 2023 May 18;21(7):1482-1487
pubmed: 36100993
Front Immunol. 2021 Jun 18;12:683026
pubmed: 34220831
Transl Neurodegener. 2020 Nov 26;9(1):42
pubmed: 33239064
Nat Rev Immunol. 2019 Aug;19(8):477-489
pubmed: 31036962
Int J Mol Sci. 2019 May 09;20(9):
pubmed: 31075861
Front Cell Neurosci. 2021 Sep 28;15:753832
pubmed: 34650406
Fitoterapia. 2015 Jun;103:231-41
pubmed: 25917513
PLoS One. 2013;8(2):e56293
pubmed: 23393609
J Bone Miner Res. 1997 Sep;12(9):1358-67
pubmed: 9286751
Inflamm Res. 2022 Aug;71(7-8):741-758
pubmed: 35612604
Ann N Y Acad Sci. 2014 Jun;1319:82-95
pubmed: 24840700
Biochem Biophys Res Commun. 2012 Feb 10;418(2):359-65
pubmed: 22269142
J Cereb Blood Flow Metab. 2009 Mar;29(3):534-44
pubmed: 19066616
J Psychiatr Res. 2019 Aug;115:90-102
pubmed: 31125917
ACS Chem Neurosci. 2023 Oct 18;14(20):3869-3882
pubmed: 37775304
Am J Physiol Cell Physiol. 2022 May 1;322(5):C939-C947
pubmed: 35385323
Glia. 2014 Jun;62(6):999-1013
pubmed: 24659539
Immunity. 2021 Oct 12;54(10):2194-2208
pubmed: 34644556
Mol Neurobiol. 2019 Sep;56(9):6184-6196
pubmed: 30734229
Semin Cell Dev Biol. 2019 Oct;94:112-120
pubmed: 31077796
Biochim Biophys Acta Mol Cell Res. 2019 Feb;1866(2):305-316
pubmed: 30521870
Exp Neurol. 2004 Oct;189(2):241-51
pubmed: 15380476
J Med Chem. 2022 Mar 24;65(6):5004-5028
pubmed: 35257581