Cell type-specific roles of PAR1 in Coxsackievirus B3 infection.
Animals
Autophagy
Cell Line
Chemokine CXCL10
/ metabolism
Coxsackievirus Infections
/ virology
Enterovirus B, Human
/ metabolism
Fibroblasts
/ metabolism
Gene Deletion
Humans
Immunity, Innate
Inflammation
Inflammation Mediators
Macrophages
/ immunology
Male
Mice
Myocarditis
/ metabolism
Myocardium
/ immunology
Myocytes, Cardiac
/ metabolism
Rats
Receptors, Proteinase-Activated
/ metabolism
Thrombin
/ metabolism
Virus Replication
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
12 07 2021
12 07 2021
Historique:
received:
09
10
2020
accepted:
14
06
2021
entrez:
13
7
2021
pubmed:
14
7
2021
medline:
15
12
2021
Statut:
epublish
Résumé
Protease-activated receptor 1 (PAR1) is widely expressed in humans and mice, and is activated by a variety of proteases, including thrombin. Recently, we showed that PAR1 contributes to the innate immune response to viral infection. Mice with a global deficiency of PAR1 expressed lower levels of CXCL10 and had increased Coxsackievirus B3 (CVB3)-induced myocarditis compared with control mice. In this study, we determined the effect of cell type-specific deletion of PAR1 in cardiac myocytes (CMs) and cardiac fibroblasts (CFs) on CVB3-induced myocarditis. Mice lacking PAR1 in either CMs or CFs exhibited increased CVB3 genomes, inflammatory infiltrates, macrophages and inflammatory mediators in the heart and increased CVB3-induced myocarditis compared with wild-type controls. Interestingly, PAR1 enhanced poly I:C induction of CXCL10 in rat CFs but not in rat neonatal CMs. Importantly, activation of PAR1 reduced CVB3 replication in murine embryonic fibroblasts and murine embryonic cardiac myocytes. In addition, we showed that PAR1 reduced autophagy in murine embryonic fibroblasts and rat H9c2 cells, which may explain how PAR1 reduces CVB3 replication. These data suggest that PAR1 on CFs protects against CVB3-induced myocarditis by enhancing the anti-viral response whereas PAR1 on both CMs and fibroblasts inhibits viral replication.
Identifiants
pubmed: 34253819
doi: 10.1038/s41598-021-93759-8
pii: 10.1038/s41598-021-93759-8
pmc: PMC8275627
doi:
Substances chimiques
Chemokine CXCL10
0
Cxcl10 protein, mouse
0
Inflammation Mediators
0
Receptors, Proteinase-Activated
0
Thrombin
EC 3.4.21.5
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
14264Subventions
Organisme : NCI NIH HHS
ID : R01 CA193678
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA204058
Pays : United States
Organisme : NIH HHS
ID : HL142799
Pays : United States
Organisme : NIH HHS
ID : HL147149
Pays : United States
Informations de copyright
© 2021. The Author(s).
Références
Sci Signal. 2012 Jul 17;5(233):ra50
pubmed: 22810896
J Clin Invest. 2013 Jan;123(1):206-14
pubmed: 23202729
J Am Coll Cardiol. 2018 May 8;71(18):1999-2010
pubmed: 29724354
J Biol Chem. 2013 Feb 8;288(6):3918-28
pubmed: 23239877
J Thromb Haemost. 2021 Apr;19(4):1103-1111
pubmed: 33346953
Thromb Haemost. 1996 Dec;76(6):860-6
pubmed: 8972001
Basic Res Cardiol. 2007 Jul;102(4):350-8
pubmed: 17468933
Microbes Infect. 2020 Jan - Feb;22(1):46-54
pubmed: 31319178
J Biol Chem. 2017 Feb 10;292(6):2065-2079
pubmed: 27994061
Cell Death Differ. 2019 Jun;26(6):1062-1076
pubmed: 30154446
Circulation. 2003 Jun 10;107(22):2793-8
pubmed: 12771005
J Mol Endocrinol. 2016 Nov;57(4):R143-R152
pubmed: 27620875
PLoS One. 2009;4(1):e4127
pubmed: 19122812
Biomed Pharmacother. 2017 Jul;91:673-679
pubmed: 28499238
Adv Drug Deliv Rev. 2008 Apr 29;60(7):786-94
pubmed: 18280610
J Virol. 2005 Mar;79(5):2979-87
pubmed: 15709018
Blood. 2013 Jan 17;121(3):431-9
pubmed: 23086754
J Am Coll Cardiol. 2012 Oct 2;60(14):1295-6
pubmed: 23017536
Blood. 2014 Apr 24;123(17):2605-13
pubmed: 24632711
Exp Cell Res. 2016 Dec 10;349(2):255-263
pubmed: 27793649
J Clin Invest. 2013 Mar;123(3):1310-22
pubmed: 23391721
Mediators Inflamm. 2014;2014:519528
pubmed: 25374444
J Virol. 2008 Aug;82(16):8149-60
pubmed: 18550677
Cardiology. 2017;136(4):258-268
pubmed: 27880950
Proc Natl Acad Sci U S A. 2008 Dec 23;105(51):20446-51
pubmed: 19074283
J Thromb Haemost. 2020 Jan;18(1):91-103
pubmed: 31539206
J Mol Cell Cardiol. 2017 Oct;111:102-113
pubmed: 28822807
Circulation. 2001 Feb 6;103(5):756-61
pubmed: 11156890
Elife. 2015 Mar 30;4:e06734
pubmed: 25821988
J Immunol. 2011 Feb 15;186(4):2561-70
pubmed: 21239721
Differentiation. 2016 Sep;92(3):66-83
pubmed: 27342817
Eur Heart J. 2011 Nov;32(21):2616-25
pubmed: 21705357
Isr Med Assoc J. 2013 Mar;15(3):180-5
pubmed: 23662385
J Thromb Haemost. 2007 May;5(5):1055-61
pubmed: 17461934
Circulation. 2007 Nov 13;116(20):2298-306
pubmed: 17967980
Circulation. 2004 Dec 7;110(23):3540-3
pubmed: 15249500
Circ Res. 2002 Sep 20;91(6):532-9
pubmed: 12242272
Circulation. 2012 Jun 19;125(24):2993-3003
pubmed: 22610965
Am J Physiol Heart Circ Physiol. 2007 Jul;293(1):H69-76
pubmed: 17434974
Cell Immunol. 2019 Oct;344:103949
pubmed: 31337508
J Am Coll Cardiol. 2013 Nov 5;62(19):1737-45
pubmed: 23871888
Nature. 2000 Sep 14;407(6801):258-64
pubmed: 11001069
Viruses. 2014 Dec 12;6(12):4999-5027
pubmed: 25514371
BMJ Open Sci. 2020 Jul 20;4(1):e100115
pubmed: 34095516
J Mol Cell Cardiol. 2018 Sep;122:80-87
pubmed: 30098988
Viruses. 2016 Jan 27;8(2):
pubmed: 26828514
J Innate Immun. 2017;9(2):181-192
pubmed: 27820939
Lab Invest. 1998 Oct;78(10):1227-37
pubmed: 9800948
Circ Res. 2000 May 26;86(10):1054-61
pubmed: 10827135
Future Microbiol. 2015;10(4):629-53
pubmed: 25865198
Clin Dev Immunol. 2012;2012:129486
pubmed: 22013485
Nature. 2001 Sep 6;413(6851):74-8
pubmed: 11544528
Basic Res Cardiol. 2014 May;109(3):408
pubmed: 24691762
J Clin Invest. 1992 Apr;89(4):1350-3
pubmed: 1313452
Int J Cardiol. 2017 Apr 1;232:40-47
pubmed: 28159361
Curr Opin Immunol. 2013 Feb;25(1):19-33
pubmed: 23290562
Genesis. 2011 Nov;49(11):870-7
pubmed: 21432986
J Mol Cell Cardiol. 2008 Jul;45(1):118-26
pubmed: 18495150
J Biol Chem. 1999 Apr 9;274(15):10066-70
pubmed: 10187786
J Cardiovasc Transl Res. 2014 Mar;7(2):203-11
pubmed: 24203054