神经炎症
TLR4型
SOCS3
小胶质细胞
细胞因子信号抑制因子1
医学
炎症
细胞因子
药理学
促炎细胞因子
受体
信号转导
免疫学
细胞生物学
生物
内科学
抑制器
癌症
车站3
作者
Yixin Fan,Cheng Qian,Bingqian Liu,Chao-Yu Wang,Haijiao Liu,Xiu-Xiu Pan,Peng Teng,Liang Hu,Guangqin Zhang,Yuan Han,Mi Yang,Xuefeng Wu,Wentao Li
标识
DOI:10.1016/j.bbi.2017.10.006
摘要
Postoperative pain is a common form of acute pain that, if not managed effectively, can become chronic pain. Evidence has shown that glia, especially microglia, mediate neuroinflammation, which plays a vital role in pain sensitization. Moreover, toll-like receptor 4 (TLR4), the tumor necrosis factor receptor (TNF-R), the interleukin-1 receptor (IL-1R), and the interleukin-6 receptor (IL-6R) have been considered key components in central pain sensitization and neuroinflammation. Therefore, we hypothesized that activation of the body's endogenous "immune brakes" will inhibit these receptors and achieve inflammation tolerance as well as relieve postoperative pain. After searching for potential candidates to serve as this immune brake, we identified and focused on the suppressor of cytokine signaling 3 (SOCS3) gene. To regulate SOCS3 expression, we used paeoniflorin to induce heat shock protein 70 (HSP70)/TLR4 signaling. We found that paeoniflorin significantly induced SOCS3 expression both in vitro and in vivo and promoted the efflux of HSP70 from the cytoplasm to the extracellular environment. Furthermore, paeoniflorin markedly attenuated incision-induced mechanical allodynia, and this effect was abolished by small interfering RNAs targeting SOCS3. These findings demonstrated an effective and safe strategy to alleviate postoperative pain.
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