Expression and functionality of Toll-like receptor 3 in the megakaryocytic lineage
- Autores
- D'Atri, Lina Paola; Etulain, Julia; Rivadeneyra, Leonardo; Lapponi, María José; Centurion, M.; Cheng, K.; Yin, H.; Schattner, Mirta Ana
- Año de publicación
- 2015
- Idioma
- inglés
- Tipo de recurso
- artículo
- Estado
- versión publicada
- Descripción
- Background: In addition to their key role in hemostasis, platelets and megakaryocytes regulate immune and inflammatory responses, in part through their expression of Toll-like receptors (TLRs). Among the TLRs, TLR3 recognizes dsRNA associated with viral infection. Thrombocytopenia is a frequent complication of viral infection. However, the expression and functionality of TLR3 in megakaryocytes and platelets is not yet well understood. Objective: To study the expression and functionality of TLR3 in the megakaryocytic lineage. Methods and results: RT-PCR, flow cytometric and immunofluorescence assays showed that TLR3 is expressed in CD34+ cells, megakaryocytes, and platelets. Immunoblotting assays showed that stimulation of megakaryocytes with two synthetic agonists of TLR3, Poly(I:C) and Poly(A:U), activated the nuclear factor-κB (NF-κB), phosphoinositide 3-kinase (PI3K)/Akt, extracellular signal-related kinase (ERK)1/2 and p38 pathways. TLR3-megakaryocyte activation resulted in reduced platelet production in vitro and interferon-β release through the PI3K-Akt and NF-κB signaling pathways. TLR3 ligands potentiated the aggregation mediated by classic platelet agonists. This effect was also observed for ATP release, but not for P-selectin or CD40L membrane exposure, indicating that TLR3 activation was not involved in α-granule release. In addition, TLR3 agonists induced activation of the NF-κB, PI3K-Akt and ERK1/2 pathways in platelets. Reductions in platelet production and platelet fibrinogen binding mediated by Poly(I:C) or Poly(A:U) were prevented by the presence of an inhibitor of the TLR3-dsRNA complex. Conclusions: Our findings indicate that functional TLR3 is expressed in CD34+ cells, megakaryocytes, and platelets, and suggest a potential role for this receptor in the megakaryopoiesis/thrombopoiesis alterations that occur in viral infections.
Fil: D'Atri, Lina Paola. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Etulain, Julia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Rivadeneyra, Leonardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Lapponi, María José. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Centurion, M.. Ciudad Autónoma de Buenos Aires. Hospital Bernardino Rivadavia ; Argentina
Fil: Cheng, K.. Tsinghua University; China
Fil: Yin, H.. Tsinghua University; China. State University of Colorado Boulder; Estados Unidos
Fil: Schattner, Mirta Ana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina - Materia
-
Interferon-Beta
Megakaryocytes
Nf-Kappa B
Platelets
Toll-Like Receptor&Nbsp;3 - Nivel de accesibilidad
- acceso abierto
- Condiciones de uso
- https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
- Repositorio
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/38495
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oai:ri.conicet.gov.ar:11336/38495 |
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CONICET Digital (CONICET) |
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Expression and functionality of Toll-like receptor 3 in the megakaryocytic lineageD'Atri, Lina PaolaEtulain, JuliaRivadeneyra, LeonardoLapponi, María JoséCenturion, M.Cheng, K.Yin, H.Schattner, Mirta AnaInterferon-BetaMegakaryocytesNf-Kappa BPlateletsToll-Like Receptor&Nbsp;3https://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Background: In addition to their key role in hemostasis, platelets and megakaryocytes regulate immune and inflammatory responses, in part through their expression of Toll-like receptors (TLRs). Among the TLRs, TLR3 recognizes dsRNA associated with viral infection. Thrombocytopenia is a frequent complication of viral infection. However, the expression and functionality of TLR3 in megakaryocytes and platelets is not yet well understood. Objective: To study the expression and functionality of TLR3 in the megakaryocytic lineage. Methods and results: RT-PCR, flow cytometric and immunofluorescence assays showed that TLR3 is expressed in CD34+ cells, megakaryocytes, and platelets. Immunoblotting assays showed that stimulation of megakaryocytes with two synthetic agonists of TLR3, Poly(I:C) and Poly(A:U), activated the nuclear factor-κB (NF-κB), phosphoinositide 3-kinase (PI3K)/Akt, extracellular signal-related kinase (ERK)1/2 and p38 pathways. TLR3-megakaryocyte activation resulted in reduced platelet production in vitro and interferon-β release through the PI3K-Akt and NF-κB signaling pathways. TLR3 ligands potentiated the aggregation mediated by classic platelet agonists. This effect was also observed for ATP release, but not for P-selectin or CD40L membrane exposure, indicating that TLR3 activation was not involved in α-granule release. In addition, TLR3 agonists induced activation of the NF-κB, PI3K-Akt and ERK1/2 pathways in platelets. Reductions in platelet production and platelet fibrinogen binding mediated by Poly(I:C) or Poly(A:U) were prevented by the presence of an inhibitor of the TLR3-dsRNA complex. Conclusions: Our findings indicate that functional TLR3 is expressed in CD34+ cells, megakaryocytes, and platelets, and suggest a potential role for this receptor in the megakaryopoiesis/thrombopoiesis alterations that occur in viral infections.Fil: D'Atri, Lina Paola. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Etulain, Julia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Rivadeneyra, Leonardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Lapponi, María José. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Centurion, M.. Ciudad Autónoma de Buenos Aires. Hospital Bernardino Rivadavia ; ArgentinaFil: Cheng, K.. Tsinghua University; ChinaFil: Yin, H.. Tsinghua University; China. State University of Colorado Boulder; Estados UnidosFil: Schattner, Mirta Ana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaWiley Blackwell Publishing, Inc2015-05info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/38495D'Atri, Lina Paola; Etulain, Julia; Rivadeneyra, Leonardo; Lapponi, María José; Centurion, M.; et al.; Expression and functionality of Toll-like receptor 3 in the megakaryocytic lineage; Wiley Blackwell Publishing, Inc; Journal of Thrombosis and Haemostasis; 13; 5; 5-2015; 839-8501538-7933CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/http://onlinelibrary.wiley.com/doi/10.1111/jth.12842/abstractinfo:eu-repo/semantics/altIdentifier/doi/10.1111/jth.12842info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T10:04:17Zoai:ri.conicet.gov.ar:11336/38495instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-03 10:04:18.068CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse |
dc.title.none.fl_str_mv |
Expression and functionality of Toll-like receptor 3 in the megakaryocytic lineage |
title |
Expression and functionality of Toll-like receptor 3 in the megakaryocytic lineage |
spellingShingle |
Expression and functionality of Toll-like receptor 3 in the megakaryocytic lineage D'Atri, Lina Paola Interferon-Beta Megakaryocytes Nf-Kappa B Platelets Toll-Like Receptor&Nbsp;3 |
title_short |
Expression and functionality of Toll-like receptor 3 in the megakaryocytic lineage |
title_full |
Expression and functionality of Toll-like receptor 3 in the megakaryocytic lineage |
title_fullStr |
Expression and functionality of Toll-like receptor 3 in the megakaryocytic lineage |
title_full_unstemmed |
Expression and functionality of Toll-like receptor 3 in the megakaryocytic lineage |
title_sort |
Expression and functionality of Toll-like receptor 3 in the megakaryocytic lineage |
dc.creator.none.fl_str_mv |
D'Atri, Lina Paola Etulain, Julia Rivadeneyra, Leonardo Lapponi, María José Centurion, M. Cheng, K. Yin, H. Schattner, Mirta Ana |
author |
D'Atri, Lina Paola |
author_facet |
D'Atri, Lina Paola Etulain, Julia Rivadeneyra, Leonardo Lapponi, María José Centurion, M. Cheng, K. Yin, H. Schattner, Mirta Ana |
author_role |
author |
author2 |
Etulain, Julia Rivadeneyra, Leonardo Lapponi, María José Centurion, M. Cheng, K. Yin, H. Schattner, Mirta Ana |
author2_role |
author author author author author author author |
dc.subject.none.fl_str_mv |
Interferon-Beta Megakaryocytes Nf-Kappa B Platelets Toll-Like Receptor&Nbsp;3 |
topic |
Interferon-Beta Megakaryocytes Nf-Kappa B Platelets Toll-Like Receptor&Nbsp;3 |
purl_subject.fl_str_mv |
https://purl.org/becyt/ford/3.1 https://purl.org/becyt/ford/3 |
dc.description.none.fl_txt_mv |
Background: In addition to their key role in hemostasis, platelets and megakaryocytes regulate immune and inflammatory responses, in part through their expression of Toll-like receptors (TLRs). Among the TLRs, TLR3 recognizes dsRNA associated with viral infection. Thrombocytopenia is a frequent complication of viral infection. However, the expression and functionality of TLR3 in megakaryocytes and platelets is not yet well understood. Objective: To study the expression and functionality of TLR3 in the megakaryocytic lineage. Methods and results: RT-PCR, flow cytometric and immunofluorescence assays showed that TLR3 is expressed in CD34+ cells, megakaryocytes, and platelets. Immunoblotting assays showed that stimulation of megakaryocytes with two synthetic agonists of TLR3, Poly(I:C) and Poly(A:U), activated the nuclear factor-κB (NF-κB), phosphoinositide 3-kinase (PI3K)/Akt, extracellular signal-related kinase (ERK)1/2 and p38 pathways. TLR3-megakaryocyte activation resulted in reduced platelet production in vitro and interferon-β release through the PI3K-Akt and NF-κB signaling pathways. TLR3 ligands potentiated the aggregation mediated by classic platelet agonists. This effect was also observed for ATP release, but not for P-selectin or CD40L membrane exposure, indicating that TLR3 activation was not involved in α-granule release. In addition, TLR3 agonists induced activation of the NF-κB, PI3K-Akt and ERK1/2 pathways in platelets. Reductions in platelet production and platelet fibrinogen binding mediated by Poly(I:C) or Poly(A:U) were prevented by the presence of an inhibitor of the TLR3-dsRNA complex. Conclusions: Our findings indicate that functional TLR3 is expressed in CD34+ cells, megakaryocytes, and platelets, and suggest a potential role for this receptor in the megakaryopoiesis/thrombopoiesis alterations that occur in viral infections. Fil: D'Atri, Lina Paola. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina Fil: Etulain, Julia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina Fil: Rivadeneyra, Leonardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina Fil: Lapponi, María José. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina Fil: Centurion, M.. Ciudad Autónoma de Buenos Aires. Hospital Bernardino Rivadavia ; Argentina Fil: Cheng, K.. Tsinghua University; China Fil: Yin, H.. Tsinghua University; China. State University of Colorado Boulder; Estados Unidos Fil: Schattner, Mirta Ana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina |
description |
Background: In addition to their key role in hemostasis, platelets and megakaryocytes regulate immune and inflammatory responses, in part through their expression of Toll-like receptors (TLRs). Among the TLRs, TLR3 recognizes dsRNA associated with viral infection. Thrombocytopenia is a frequent complication of viral infection. However, the expression and functionality of TLR3 in megakaryocytes and platelets is not yet well understood. Objective: To study the expression and functionality of TLR3 in the megakaryocytic lineage. Methods and results: RT-PCR, flow cytometric and immunofluorescence assays showed that TLR3 is expressed in CD34+ cells, megakaryocytes, and platelets. Immunoblotting assays showed that stimulation of megakaryocytes with two synthetic agonists of TLR3, Poly(I:C) and Poly(A:U), activated the nuclear factor-κB (NF-κB), phosphoinositide 3-kinase (PI3K)/Akt, extracellular signal-related kinase (ERK)1/2 and p38 pathways. TLR3-megakaryocyte activation resulted in reduced platelet production in vitro and interferon-β release through the PI3K-Akt and NF-κB signaling pathways. TLR3 ligands potentiated the aggregation mediated by classic platelet agonists. This effect was also observed for ATP release, but not for P-selectin or CD40L membrane exposure, indicating that TLR3 activation was not involved in α-granule release. In addition, TLR3 agonists induced activation of the NF-κB, PI3K-Akt and ERK1/2 pathways in platelets. Reductions in platelet production and platelet fibrinogen binding mediated by Poly(I:C) or Poly(A:U) were prevented by the presence of an inhibitor of the TLR3-dsRNA complex. Conclusions: Our findings indicate that functional TLR3 is expressed in CD34+ cells, megakaryocytes, and platelets, and suggest a potential role for this receptor in the megakaryopoiesis/thrombopoiesis alterations that occur in viral infections. |
publishDate |
2015 |
dc.date.none.fl_str_mv |
2015-05 |
dc.type.none.fl_str_mv |
info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion http://purl.org/coar/resource_type/c_6501 info:ar-repo/semantics/articulo |
format |
article |
status_str |
publishedVersion |
dc.identifier.none.fl_str_mv |
http://hdl.handle.net/11336/38495 D'Atri, Lina Paola; Etulain, Julia; Rivadeneyra, Leonardo; Lapponi, María José; Centurion, M.; et al.; Expression and functionality of Toll-like receptor 3 in the megakaryocytic lineage; Wiley Blackwell Publishing, Inc; Journal of Thrombosis and Haemostasis; 13; 5; 5-2015; 839-850 1538-7933 CONICET Digital CONICET |
url |
http://hdl.handle.net/11336/38495 |
identifier_str_mv |
D'Atri, Lina Paola; Etulain, Julia; Rivadeneyra, Leonardo; Lapponi, María José; Centurion, M.; et al.; Expression and functionality of Toll-like receptor 3 in the megakaryocytic lineage; Wiley Blackwell Publishing, Inc; Journal of Thrombosis and Haemostasis; 13; 5; 5-2015; 839-850 1538-7933 CONICET Digital CONICET |
dc.language.none.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
info:eu-repo/semantics/altIdentifier/url/http://onlinelibrary.wiley.com/doi/10.1111/jth.12842/abstract info:eu-repo/semantics/altIdentifier/doi/10.1111/jth.12842 |
dc.rights.none.fl_str_mv |
info:eu-repo/semantics/openAccess https://creativecommons.org/licenses/by-nc-sa/2.5/ar/ |
eu_rights_str_mv |
openAccess |
rights_invalid_str_mv |
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/ |
dc.format.none.fl_str_mv |
application/pdf application/pdf application/pdf application/pdf application/pdf application/pdf |
dc.publisher.none.fl_str_mv |
Wiley Blackwell Publishing, Inc |
publisher.none.fl_str_mv |
Wiley Blackwell Publishing, Inc |
dc.source.none.fl_str_mv |
reponame:CONICET Digital (CONICET) instname:Consejo Nacional de Investigaciones Científicas y Técnicas |
reponame_str |
CONICET Digital (CONICET) |
collection |
CONICET Digital (CONICET) |
instname_str |
Consejo Nacional de Investigaciones Científicas y Técnicas |
repository.name.fl_str_mv |
CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas |
repository.mail.fl_str_mv |
dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar |
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1842269849205604352 |
score |
13.13397 |