Extracellular Hsp70 inhibits pro-inflammatory cytokine production by IL-10 driven down-regulation of C/EBPβ and C/EBPδ. (28th June 2013)

• Record Type: Journal Article
• Authors: Borges, Thiago J.; Lopes, Rafael L.; Pinho, Nathana G.; Machado, Felipe D.; Souza, Ana Paula D.; Bonorino, Cristina
• Is Part Of: International journal of hyperthermia. Volume 29:Number 5(2013)
• Page Start: 455
• Page End: 463
• Publication Date: 2013-06-28
• Subjects: Hsp70 -- C/EBPβ -- C/EBPδ -- immunomodulation -- dendritic cells; Thermotherapy -- Periodicals; 615.832
• DOI: 10.3109/02656736.2013.798037
• Languages: English
• ISSNs: 0265-6736

Abstract

Abstract: Purpose : Extracellular Hsp70 has anti-inflammatory potential, demonstrated in different models of inflammatory diseases. We investigated probable mechanisms used by Hsp70 to down-regulate pro-inflammatory cytokines. Materials and methods : We analysed cytokine mRNA levels in bone marrow-derived murine dendritic cells treated with Hsp70, lipopolysaccharide (LPS) and peptidoglycan (PGN) or OVA (an irrelevant protein control), hypothesising that this was mediated by C/EBPβ and C/EBPδ transcription factors. We also tested the involvement of TLR2, IL-10, ERK and STAT3, using genetically deficient mice and pharmacological inhibitors. Results : C/EBPβ and C/EBPδ levels were inhibited in bone marrow derived dendritic cells (BMDCs) treated with Hsp70, and that correlated with inhibition of TNF-α, IFN-γ and MCP-1. Such inhibition was not observed in TLR2 or IL-10 knockout mice, and was also abrogated upon pretreatment of cells with ERK and JAK2/STAT3 inhibitors. Conclusions : C/EBPβ and C/EBPδ transcription factors are inhibited by Hsp70 treatment, and their inhibition occurs via the TLR2-ERK-STAT3-IL-10 pathway in BMDCs, mediating the anti-inflammatory effects of Hsp70.