Cargando…

Heat shock protein 70 down-regulates the production of toll-like receptor-induced pro-inflammatory cytokines by a heat shock factor-1/constitutive heat shock element-binding factor-dependent mechanism

BACKGROUND: Heat shock protein 70 (Hsp70) is an intracellular chaperone protein with regulatory and cytoprotective functions. Hsp70 can also be found in the extracellular milieu, as a result of active secretion or passive release from damaged cells. The role of extracellular Hsp70 is not fully under...

Descripción completa

Detalles Bibliográficos
Autores principales: Ferat-Osorio, Eduardo, Sánchez-Anaya, Aldair, Gutiérrez-Mendoza, Mireille, Boscó-Gárate, Ilka, Wong-Baeza, Isabel, Pastelin-Palacios, Rodolfo, Pedraza-Alva, Gustavo, Bonifaz, Laura C, Cortés-Reynosa, Pedro, Pérez-Salazar, Eduardo, Arriaga-Pizano, Lourdes, López-Macías, Constantino, Rosenstein, Yvonne, Isibasi, Armando
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4105516/
https://www.ncbi.nlm.nih.gov/pubmed/25053922
http://dx.doi.org/10.1186/1476-9255-11-19
_version_ 1782327380634763264
author Ferat-Osorio, Eduardo
Sánchez-Anaya, Aldair
Gutiérrez-Mendoza, Mireille
Boscó-Gárate, Ilka
Wong-Baeza, Isabel
Pastelin-Palacios, Rodolfo
Pedraza-Alva, Gustavo
Bonifaz, Laura C
Cortés-Reynosa, Pedro
Pérez-Salazar, Eduardo
Arriaga-Pizano, Lourdes
López-Macías, Constantino
Rosenstein, Yvonne
Isibasi, Armando
author_facet Ferat-Osorio, Eduardo
Sánchez-Anaya, Aldair
Gutiérrez-Mendoza, Mireille
Boscó-Gárate, Ilka
Wong-Baeza, Isabel
Pastelin-Palacios, Rodolfo
Pedraza-Alva, Gustavo
Bonifaz, Laura C
Cortés-Reynosa, Pedro
Pérez-Salazar, Eduardo
Arriaga-Pizano, Lourdes
López-Macías, Constantino
Rosenstein, Yvonne
Isibasi, Armando
author_sort Ferat-Osorio, Eduardo
collection PubMed
description BACKGROUND: Heat shock protein 70 (Hsp70) is an intracellular chaperone protein with regulatory and cytoprotective functions. Hsp70 can also be found in the extracellular milieu, as a result of active secretion or passive release from damaged cells. The role of extracellular Hsp70 is not fully understood. Some studies report that it activates monocytes, macrophages and dendritic cells through innate immune receptors (such as Toll-like receptors, TLRs), while others report that Hsp70 is a negative regulator of the inflammatory response. In order to address this apparent inconsistency, in this study we evaluated the response of human monocytes to a highly purified recombinant Hsp70. METHODS: Human peripheral blood monocytes were stimulated with Hsp70, alone or in combination with TLR agonists. Cytokines were quantified in culture supernatants, their mRNAs were measured by RT-PCR, and the binding of transcription factors was evaluated by electrophoretic mobility shift assay (EMSA). Kruskal-Wallis test or one-way or two-way ANOVA were used to analyze the data. RESULTS: The addition of Hsp70 to TLR-activated monocytes down-regulated TNF-α as well as IL-6 levels. This effect was independent of a physical interaction between Hsp70 and TLR agonists; instead it resulted of changes at the TNF-α gene expression level. The decrease in TNF-α expression correlated with the binding of HSF-1 (heat shock transcription factor 1, a transcription factor activated in response to Hsp70) and CHBF (constitutive HSE-binding factor) to the TNF-α gene promoter. CONCLUSION: Extracellular Hsp70 negatively regulates the production of pro-inflammatory cytokines of monocytes exposed to TLR agonists and contributes to dampen the inflammatory response.
format Online
Article
Text
id pubmed-4105516
institution National Center for Biotechnology Information
language English
publishDate 2014
publisher BioMed Central
record_format MEDLINE/PubMed
spelling pubmed-41055162014-07-23 Heat shock protein 70 down-regulates the production of toll-like receptor-induced pro-inflammatory cytokines by a heat shock factor-1/constitutive heat shock element-binding factor-dependent mechanism Ferat-Osorio, Eduardo Sánchez-Anaya, Aldair Gutiérrez-Mendoza, Mireille Boscó-Gárate, Ilka Wong-Baeza, Isabel Pastelin-Palacios, Rodolfo Pedraza-Alva, Gustavo Bonifaz, Laura C Cortés-Reynosa, Pedro Pérez-Salazar, Eduardo Arriaga-Pizano, Lourdes López-Macías, Constantino Rosenstein, Yvonne Isibasi, Armando J Inflamm (Lond) Research BACKGROUND: Heat shock protein 70 (Hsp70) is an intracellular chaperone protein with regulatory and cytoprotective functions. Hsp70 can also be found in the extracellular milieu, as a result of active secretion or passive release from damaged cells. The role of extracellular Hsp70 is not fully understood. Some studies report that it activates monocytes, macrophages and dendritic cells through innate immune receptors (such as Toll-like receptors, TLRs), while others report that Hsp70 is a negative regulator of the inflammatory response. In order to address this apparent inconsistency, in this study we evaluated the response of human monocytes to a highly purified recombinant Hsp70. METHODS: Human peripheral blood monocytes were stimulated with Hsp70, alone or in combination with TLR agonists. Cytokines were quantified in culture supernatants, their mRNAs were measured by RT-PCR, and the binding of transcription factors was evaluated by electrophoretic mobility shift assay (EMSA). Kruskal-Wallis test or one-way or two-way ANOVA were used to analyze the data. RESULTS: The addition of Hsp70 to TLR-activated monocytes down-regulated TNF-α as well as IL-6 levels. This effect was independent of a physical interaction between Hsp70 and TLR agonists; instead it resulted of changes at the TNF-α gene expression level. The decrease in TNF-α expression correlated with the binding of HSF-1 (heat shock transcription factor 1, a transcription factor activated in response to Hsp70) and CHBF (constitutive HSE-binding factor) to the TNF-α gene promoter. CONCLUSION: Extracellular Hsp70 negatively regulates the production of pro-inflammatory cytokines of monocytes exposed to TLR agonists and contributes to dampen the inflammatory response. BioMed Central 2014-07-12 /pmc/articles/PMC4105516/ /pubmed/25053922 http://dx.doi.org/10.1186/1476-9255-11-19 Text en Copyright © 2014 Ferat-Osorio et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Ferat-Osorio, Eduardo
Sánchez-Anaya, Aldair
Gutiérrez-Mendoza, Mireille
Boscó-Gárate, Ilka
Wong-Baeza, Isabel
Pastelin-Palacios, Rodolfo
Pedraza-Alva, Gustavo
Bonifaz, Laura C
Cortés-Reynosa, Pedro
Pérez-Salazar, Eduardo
Arriaga-Pizano, Lourdes
López-Macías, Constantino
Rosenstein, Yvonne
Isibasi, Armando
Heat shock protein 70 down-regulates the production of toll-like receptor-induced pro-inflammatory cytokines by a heat shock factor-1/constitutive heat shock element-binding factor-dependent mechanism
title Heat shock protein 70 down-regulates the production of toll-like receptor-induced pro-inflammatory cytokines by a heat shock factor-1/constitutive heat shock element-binding factor-dependent mechanism
title_full Heat shock protein 70 down-regulates the production of toll-like receptor-induced pro-inflammatory cytokines by a heat shock factor-1/constitutive heat shock element-binding factor-dependent mechanism
title_fullStr Heat shock protein 70 down-regulates the production of toll-like receptor-induced pro-inflammatory cytokines by a heat shock factor-1/constitutive heat shock element-binding factor-dependent mechanism
title_full_unstemmed Heat shock protein 70 down-regulates the production of toll-like receptor-induced pro-inflammatory cytokines by a heat shock factor-1/constitutive heat shock element-binding factor-dependent mechanism
title_short Heat shock protein 70 down-regulates the production of toll-like receptor-induced pro-inflammatory cytokines by a heat shock factor-1/constitutive heat shock element-binding factor-dependent mechanism
title_sort heat shock protein 70 down-regulates the production of toll-like receptor-induced pro-inflammatory cytokines by a heat shock factor-1/constitutive heat shock element-binding factor-dependent mechanism
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4105516/
https://www.ncbi.nlm.nih.gov/pubmed/25053922
http://dx.doi.org/10.1186/1476-9255-11-19
work_keys_str_mv AT feratosorioeduardo heatshockprotein70downregulatestheproductionoftolllikereceptorinducedproinflammatorycytokinesbyaheatshockfactor1constitutiveheatshockelementbindingfactordependentmechanism
AT sanchezanayaaldair heatshockprotein70downregulatestheproductionoftolllikereceptorinducedproinflammatorycytokinesbyaheatshockfactor1constitutiveheatshockelementbindingfactordependentmechanism
AT gutierrezmendozamireille heatshockprotein70downregulatestheproductionoftolllikereceptorinducedproinflammatorycytokinesbyaheatshockfactor1constitutiveheatshockelementbindingfactordependentmechanism
AT boscogarateilka heatshockprotein70downregulatestheproductionoftolllikereceptorinducedproinflammatorycytokinesbyaheatshockfactor1constitutiveheatshockelementbindingfactordependentmechanism
AT wongbaezaisabel heatshockprotein70downregulatestheproductionoftolllikereceptorinducedproinflammatorycytokinesbyaheatshockfactor1constitutiveheatshockelementbindingfactordependentmechanism
AT pastelinpalaciosrodolfo heatshockprotein70downregulatestheproductionoftolllikereceptorinducedproinflammatorycytokinesbyaheatshockfactor1constitutiveheatshockelementbindingfactordependentmechanism
AT pedrazaalvagustavo heatshockprotein70downregulatestheproductionoftolllikereceptorinducedproinflammatorycytokinesbyaheatshockfactor1constitutiveheatshockelementbindingfactordependentmechanism
AT bonifazlaurac heatshockprotein70downregulatestheproductionoftolllikereceptorinducedproinflammatorycytokinesbyaheatshockfactor1constitutiveheatshockelementbindingfactordependentmechanism
AT cortesreynosapedro heatshockprotein70downregulatestheproductionoftolllikereceptorinducedproinflammatorycytokinesbyaheatshockfactor1constitutiveheatshockelementbindingfactordependentmechanism
AT perezsalazareduardo heatshockprotein70downregulatestheproductionoftolllikereceptorinducedproinflammatorycytokinesbyaheatshockfactor1constitutiveheatshockelementbindingfactordependentmechanism
AT arriagapizanolourdes heatshockprotein70downregulatestheproductionoftolllikereceptorinducedproinflammatorycytokinesbyaheatshockfactor1constitutiveheatshockelementbindingfactordependentmechanism
AT lopezmaciasconstantino heatshockprotein70downregulatestheproductionoftolllikereceptorinducedproinflammatorycytokinesbyaheatshockfactor1constitutiveheatshockelementbindingfactordependentmechanism
AT rosensteinyvonne heatshockprotein70downregulatestheproductionoftolllikereceptorinducedproinflammatorycytokinesbyaheatshockfactor1constitutiveheatshockelementbindingfactordependentmechanism
AT isibasiarmando heatshockprotein70downregulatestheproductionoftolllikereceptorinducedproinflammatorycytokinesbyaheatshockfactor1constitutiveheatshockelementbindingfactordependentmechanism