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Arthritis Research & Therapy
Published in: Arthritis Research & Therapy 2/2008

Open Access 01-04-2008 | Research article

Extracellular heat shock protein 70 inhibits tumour necrosis factor-α induced proinflammatory mediator production in fibroblast-like synoviocytes

Authors: Xinjing Luo, Xiaoxia Zuo, Yaou Zhou, Bing Zhang, Yongzhong Shi, Meidong Liu, Kangkai Wang, D Randy McMillian, Xianzhong Xiao

Published in: Arthritis Research & Therapy | Issue 2/2008

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Abstract

Introduction

It was recently suggested that heat shock protein (HSP)70, an intracellular protein, is a potential mediator of inflammatory disease when it is released into the extracellular compartment. Although elevated HSP70 levels have been identified in rheumatoid arthritis (RA) synovial tissues and RA synovial fluid compared with patients with osteoarthritis and healthy individuals, it remains unclear what role extracellular HSP70 plays in the pathogenesis of RA. This study was conducted to investigate the effects of extracellular HSP70 on the production of RA-associated cytokines in fibroblast-like synoviocytes from patients with RA and to elucidate the mechanisms involved.

Methods

IL-6, IL-8 and monocyte chemoattractant protein (MCP)-1 levels in culture supernatants were measured using enzyme-linked immunosorbent assays. Activation of mitogen-activated protein kinases (MAPKs), such as extracellular signal-regulated protein kinases (ERKs), c-Jun amino-terminal kinase (JNK) and p38 MAPK, was detected using Western blotting. Nuclear translocation of nuclear factor-κB (NF-κB) and degradation of the inhibitory protein IκBα were examined using immunohistochemistry and Western blotting.

Results

Human HSP70 downregulated IL-6, IL-8 and MCP-1 production in RA fibroblast-like synoviocytes induced by tumour necrosis factor (TNF)-α in a concentration dependent manner. HSP70 inhibited the activation of ERK, JNK and p38 MAPK in fibroblast-like synoviocytes stimulated by TNF-α. Furthermore, HSP70 also significantly inhibited nuclear translocation of nuclear factor-κB and degradation of IκBα induced by TNF-α.

Conclusion

Extracellular HSP70 has an anti-inflammatory effect on RA by downregulating production of IL-6, IL-8 and MCP-1 in fibroblast-like synoviocytes, which is mediated through inhibited activation of the MAPKs and NF-κB signal pathways.
Appendix
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Metadata
Title
Extracellular heat shock protein 70 inhibits tumour necrosis factor-α induced proinflammatory mediator production in fibroblast-like synoviocytes
Authors
Xinjing Luo
Xiaoxia Zuo
Yaou Zhou
Bing Zhang
Yongzhong Shi
Meidong Liu
Kangkai Wang
D Randy McMillian
Xianzhong Xiao
Publication date
01-04-2008
Publisher
BioMed Central
Published in
Arthritis Research & Therapy / Issue 2/2008
Electronic ISSN: 1478-6362
DOI
https://doi.org/10.1186/ar2399

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