Synergistic effects triggered by simultaneous Toll-like receptor-2 and -3 activation in human periodontal ligament stem cells.
Toll-like receptor 2
Toll-like receptor 3
mesenchymal stem cells
periodontal ligament
Journal
Journal of periodontology
ISSN: 1943-3670
Titre abrégé: J Periodontol
Pays: United States
ID NLM: 8000345
Informations de publication
Date de publication:
10 2019
10 2019
Historique:
received:
05
01
2019
revised:
26
03
2019
accepted:
17
04
2019
pubmed:
3
5
2019
medline:
9
4
2020
entrez:
4
5
2019
Statut:
ppublish
Résumé
Although periodontitis is associated with disruption of the host-microbial homeostasis, viruses are currently discussed to influence disease progression. Viral pathogens are recognized by Toll-like receptor (TLR)-3, which engages a different signaling pathway than other TLRs. This study aimed to investigate the effect of TLR-3 agonist polyinosinic:polycytidylic acid (Poly I:C) on the expression of inflammatory markers and bone metabolism proteins by human periodontal ligament stem cells (hPDLSCs) compared with TLR-2 agonist Pam3CSK4, which mimics the effect of bacterial lipoproteins. To assess potential combined effects of bacterial and viral infections, hPDLSCs response to simultaneous TLR-2 and TLR-3 activation was investigated. HPDLSCs were stimulated with Poly I:C (0.0001-1 µg/mL), Pam3CSK4 (1 µg/mL), and their combinations for 24 hours. Gene expression and protein levels of interleukin (IL)-6, IL-8, monocyte chemoattractant protein (MCP)-1, and osteoprotegerin (OPG) were measured with qPCR and ELISA. Production of IL-6, IL-8, MCP-1, and OPG was significantly increased by Poly I:C or Pam3CSK4 to a similar extent. The levels of all inflammatory mediators induced by simultaneous stimulation with Poly I:C and Pam3CSK4 were significantly higher compared with single stimuli as well as to their summed response. Gene expression and protein levels of OPG were enhanced by Poly I:C, but by lesser extent than by Pam3CSK4. OPG levels upon simultaneous stimulation with Pam3CSK4 and Poly I:C were significantly lower compared with Pam3CSK4 stimulation alone. Simultaneous TLR-2 and TLR-3 activation synergistically triggers IL-6, IL-8, and MCP-1 production, which was not observed for OPG. These findings suggest that TLR-3 activation by viral infections might promote periodontitis progression.
Sections du résumé
BACKGROUND
Although periodontitis is associated with disruption of the host-microbial homeostasis, viruses are currently discussed to influence disease progression. Viral pathogens are recognized by Toll-like receptor (TLR)-3, which engages a different signaling pathway than other TLRs. This study aimed to investigate the effect of TLR-3 agonist polyinosinic:polycytidylic acid (Poly I:C) on the expression of inflammatory markers and bone metabolism proteins by human periodontal ligament stem cells (hPDLSCs) compared with TLR-2 agonist Pam3CSK4, which mimics the effect of bacterial lipoproteins. To assess potential combined effects of bacterial and viral infections, hPDLSCs response to simultaneous TLR-2 and TLR-3 activation was investigated.
METHODS
HPDLSCs were stimulated with Poly I:C (0.0001-1 µg/mL), Pam3CSK4 (1 µg/mL), and their combinations for 24 hours. Gene expression and protein levels of interleukin (IL)-6, IL-8, monocyte chemoattractant protein (MCP)-1, and osteoprotegerin (OPG) were measured with qPCR and ELISA.
RESULTS
Production of IL-6, IL-8, MCP-1, and OPG was significantly increased by Poly I:C or Pam3CSK4 to a similar extent. The levels of all inflammatory mediators induced by simultaneous stimulation with Poly I:C and Pam3CSK4 were significantly higher compared with single stimuli as well as to their summed response. Gene expression and protein levels of OPG were enhanced by Poly I:C, but by lesser extent than by Pam3CSK4. OPG levels upon simultaneous stimulation with Pam3CSK4 and Poly I:C were significantly lower compared with Pam3CSK4 stimulation alone.
CONCLUSIONS
Simultaneous TLR-2 and TLR-3 activation synergistically triggers IL-6, IL-8, and MCP-1 production, which was not observed for OPG. These findings suggest that TLR-3 activation by viral infections might promote periodontitis progression.
Identifiants
pubmed: 31049957
doi: 10.1002/JPER.19-0005
pmc: PMC6852053
doi:
Substances chimiques
Interleukin-6
0
Lipopolysaccharides
0
Toll-Like Receptor 2
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1190-1201Subventions
Organisme : Austrian Science Fund FWF
ID : P 29440
Pays : Austria
Informations de copyright
© 2019 The Authors. Journal of Periodontology published by Wiley Periodicals, Inc. on behalf of American Academy of Periodontology.
Références
Stem Cells Int. 2015;2015:972313
pubmed: 25861283
Arthritis Res Ther. 2006;8 Suppl 2:S3
pubmed: 16899107
Eur J Oral Sci. 2003 Aug;111(4):346-52
pubmed: 12887401
Front Immunol. 2012 Jul 02;3:182
pubmed: 22783256
Periodontol 2000. 2015 Oct;69(1):28-45
pubmed: 26252400
Adv Immunol. 1994;55:97-179
pubmed: 8304236
Am J Pathol. 2006 Sep;169(3):987-98
pubmed: 16936272
Oral Dis. 2017 Mar;23(2):168-180
pubmed: 26923115
Clin Oral Investig. 2014 Jan;18(1):171-8
pubmed: 23404558
J Periodontal Res. 2015 Apr;50(2):141-51
pubmed: 24854880
J Immunol. 2007 Jan 15;178(2):1151-7
pubmed: 17202379
J Immunol. 2006 Dec 15;177(12):8296-300
pubmed: 17142724
Microb Pathog. 2007 Jul;43(1):46-53
pubmed: 17448630
Cell. 2007 Sep 21;130(6):1071-82
pubmed: 17889651
Mediators Inflamm. 2019 Apr 23;2019:8127301
pubmed: 31178663
J Periodontol. 2019 Apr;90(4):400-415
pubmed: 30362568
APMIS. 2009 Oct;117(10):746-54
pubmed: 19775343
J Periodontol. 2019 Oct;90(10):1190-1201
pubmed: 31049957
Biochem Biophys Res Commun. 2009 Oct 30;388(4):621-5
pubmed: 19686699
J Clin Periodontol. 2011 Apr;38(4):318-25
pubmed: 21284689
J Periodontal Res. 2013 Dec;48(6):757-65
pubmed: 23679005
Periodontol 2000. 2013 Oct;63(1):198-216
pubmed: 23931061
Infect Immun. 2004 Sep;72(9):5041-51
pubmed: 15321997
Bone. 2004 Sep;35(3):629-35
pubmed: 15336598
Immunol Lett. 2008 Feb 15;116(1):86-94
pubmed: 18166232
J Cell Biochem. 2011 Jul;112(7):1890-7
pubmed: 21433061
Sci Rep. 2017 Oct 9;7(1):12856
pubmed: 28993635
Cytokine. 2008 May;42(2):145-151
pubmed: 18304834
Periodontol 2000. 2015 Oct;69(1):255-73
pubmed: 26252412
Nat Immunol. 2010 May;11(5):373-84
pubmed: 20404851
Immunity. 2010 Mar 26;32(3):305-15
pubmed: 20346772
J Bone Miner Res. 1999 Sep;14(9):1486-92
pubmed: 10469276
Infect Immun. 2013 Apr;81(4):1277-86
pubmed: 23381996
Nat Rev Immunol. 2015 Jan;15(1):30-44
pubmed: 25534621
PLoS One. 2016 Aug 09;11(8):e0160848
pubmed: 27504628
Eur J Immunol. 2007 Nov;37(11):3040-53
pubmed: 17918201
J Mol Biol. 2014 Mar 20;426(6):1246-64
pubmed: 24316048
Int J Clin Exp Med. 2015 Apr 15;8(4):6186-92
pubmed: 26131223
J Periodontol. 2013 Sep;84(9):1353-60
pubmed: 23136947
Periodontol 2000. 2007;43:41-55
pubmed: 17214834
Mol Oral Microbiol. 2017 Jun;32(3):211-225
pubmed: 27224005
Orthod Craniofac Res. 2007 Aug;10(3):149-60
pubmed: 17651131
J Periodontal Res. 2018 Aug;53(4):589-597
pubmed: 29582430
PLoS One. 2017 Jun 29;12(6):e0180073
pubmed: 28662082
J Dent Res. 2007 Apr;86(4):306-19
pubmed: 17384024
Viruses. 2011 Jun;3(6):920-40
pubmed: 21994762
Periodontol 2000. 2017 Oct;75(1):7-23
pubmed: 28758294
Proc Natl Acad Sci U S A. 2015 Nov 10;112(45):13994-9
pubmed: 26508631
Stem Cells Dev. 2014 Oct 15;23(20):2524-34
pubmed: 24827498