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Journal of Inflammation
Published in: Journal of Inflammation 1/2014

Open Access 01-12-2014 | Research

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

Authors: Eduardo Ferat-Osorio, Aldair Sánchez-Anaya, Mireille Gutiérrez-Mendoza, Ilka Boscó-Gárate, Isabel Wong-Baeza, Rodolfo Pastelin-Palacios, Gustavo Pedraza-Alva, Laura C Bonifaz, Pedro Cortés-Reynosa, Eduardo Pérez-Salazar, Lourdes Arriaga-Pizano, Constantino López-Macías, Yvonne Rosenstein, Armando Isibasi

Published in: Journal of Inflammation | Issue 1/2014

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Abstract

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.
Appendix
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Metadata
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
Authors
Eduardo Ferat-Osorio
Aldair Sánchez-Anaya
Mireille Gutiérrez-Mendoza
Ilka Boscó-Gárate
Isabel Wong-Baeza
Rodolfo Pastelin-Palacios
Gustavo Pedraza-Alva
Laura C Bonifaz
Pedro Cortés-Reynosa
Eduardo Pérez-Salazar
Lourdes Arriaga-Pizano
Constantino López-Macías
Yvonne Rosenstein
Armando Isibasi
Publication date
01-12-2014
Publisher
BioMed Central
Published in
Journal of Inflammation / Issue 1/2014
Electronic ISSN: 1476-9255
DOI
https://doi.org/10.1186/1476-9255-11-19

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