Association of HSP22 with mTOR in osteoblasts: regulation of TNF-α-stimulated IL-6 synthesis
Association of HSP22 with mTOR in osteoblasts: regulation of TNF-α-stimulated IL-6 synthesis
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DOI：
10.1002/1873-3468.13028
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发表时间：
2018-04-01
期刊：
影响因子：
3.5
通讯作者：
Otsuka, Takanobu
中科院分区：
文献类型：
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作者：
Sakai, Go;Tokuda, Haruhiko;Otsuka, Takanobu
热休克蛋白22（HSP 22）在包括成骨细胞在内的各种类型的细胞中广泛表达。我们先前报道了肿瘤坏死因子（TNF）-α通过p44/p42 MAPK刺激成骨样MC 3 T3-E1细胞中白细胞介素（IL）-6的合成，并且mTOR/p70 S6激酶（p70 S6 K）负性调节IL-6的合成。在这项研究中，我们研究了热休克蛋白22参与TNF-α刺激的IL-6合成和MC 3 T3-E1细胞的潜在机制。HSP 22敲低减少TNF-α刺激的IL-6释放。此外，HSP 22敲低增强TNF-α诱导的p70 S6 K磷酸化，但抑制p44/p42 MAPK磷酸化。HSP 22与mTOR共免疫沉淀。HSP 22敲低增加磷酸化mTOR的基础水平。这些结果强烈表明，HSP 22与mTOR相互作用，并调节成骨细胞中TNF-α诱导的IL-6合成。
Heat shock protein 22 (HSP22) is ubiquitously expressed in various types of cells including in osteoblasts. We previously reported that tumor necrosis factor (TNF)-alpha stimulates interleukin (IL)-6 synthesis via p44/p42 MAPK in osteoblast-like MC3T3-E1 cells and that mTOR/p70 S6 kinase (p70 S6K) negatively regulates the IL-6 synthesis. In this study, we investigated the involvement of HSP22 in TNF-alpha-stimulated-IL-6 synthesis and the underlying mechanism in MC3T3-E1 cells. HSP22 knockdown reduces TNF-alpha-stimulated release of IL-6. In addition, HSP22 knockdown strengthens TNF-alpha-induced phosphorylation of p70 S6K but suppresses that of p44/p42 MAPK. HSP22 coimmunoprecipitates with mTOR. HSP22 knockdown increases the basal levels of phosphorylated mTOR. These results strongly suggest that HSP22 interacts with mTOR and regulates TNF-alpha-induced IL-6 synthesis in osteoblasts.