Extracellular heat shock protein 70 inhibits tumour necrosis factor-alpha induced proinflammatory mediator production in fibroblast-like synoviocytes.
Extracellular heat shock protein 70 inhibits tumour necrosis factor-alpha induced proinflammatory mediator production in fibroblast-like synoviocytes.
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DOI：
10.1186/ar2399
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发表时间：
2008
影响因子：
4.9
通讯作者：
Xiao X
中科院分区：
文献类型：
--
作者：
Luo X;Zuo X;Zhou Y;Zhang B;Shi Y;Liu M;Wang K;McMillian DR;Xiao X
热休克蛋白（HSP）70是一种细胞内蛋白，当它被释放到细胞外时，它是一种潜在的炎症介质。尽管与骨关节炎患者和健康个体相比，类风湿关节炎（RA）滑膜组织和RA滑液中的HSP 70水平升高，但仍不清楚细胞外HSP 70在RA发病机制中起什么作用。本研究旨在探讨细胞外热休克蛋白70对类风湿关节炎患者成纤维样滑膜细胞产生类风湿关节炎相关细胞因子的影响，并阐明其机制。采用酶联免疫吸附试验测定培养上清液中IL-6、IL-8和单核细胞趋化蛋白（MCP）-1水平。采用Western印迹法检测细胞外信号调节蛋白激酶（ERK）、c-Jun氨基末端激酶（JNK）和p38 MAPK等丝裂原活化蛋白激酶（MAPK）的活化。免疫组化和Western blotting检测核因子-κB（NF-κB）的核转位和抑制蛋白IκBα的降解。人热休克蛋白70以浓度依赖性方式下调肿瘤坏死因子（TNF）-α诱导的RA成纤维样滑膜细胞产生IL-6、IL-8和MCP-1。HSP 70可抑制TNF-α刺激的成纤维样滑膜细胞ERK、JNK和p38 MAPK的活化。HSP 70还能显著抑制TNF-α诱导的核因子-κB核转位和IκBα降解。细胞外HSP 70通过抑制成纤维细胞样滑膜细胞产生IL-6、IL-8和MCP-1，抑制MAPK和NF-κB信号通路的活化，从而发挥抗炎作用。
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. 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. 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. 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.
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影响因子：
--
作者：
Min, DJ;Cho, ML;Kim, HY
通讯作者：
Kim, HY
DOI：
10.1186/ar391
发表时间：
2002
期刊：
Arthritis research
影响因子：
--
作者：
Hirth A;Skapenko A;Kinne RW;Emmrich F;Schulze-Koops H;Sack U
通讯作者：
Sack U
影响因子：
--
作者：
Corrigall, VM;Bodman-Smith, MD;Panayi, GS
通讯作者：
Panayi, GS
影响因子：
4.6
作者：
Kingston, AE;Hicks, CA;Billingham, MEJ
通讯作者：
Billingham, MEJ
影响因子：
3.8
作者：
LOETSCHER, P;DEWALD, B;SEITZ, M
通讯作者：
SEITZ, M