CD11b-activated Src signal attenuates neuroinflammatory pain by orchestrating inflammatory and anti-inflammatory cytokines in microglia.
CD11b-activated Src signal attenuates neuroinflammatory pain by orchestrating inflammatory and anti-inflammatory cytokines in microglia.
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CD11b 激活的 Src 信号通过协调小胶质细胞中的炎症和抗炎细胞因子来减轻神经炎症疼痛
DOI：
10.1177/1744806918808150
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发表时间：
2018-01
期刊：
影响因子：
3.3
通讯作者：
Yuan H
中科院分区：
文献类型：
--
作者：
Yang M;Xu W;Wang Y;Jiang X;Li Y;Yang Y;Yuan H
神经炎症在慢性疼痛的诱导和维持中起着重要作用。模式识别受体诱导的促炎和抗炎细胞因子对炎症稳态至关重要。巨噬细胞上的CD11b可以抑制toll样受体（TLR）激活引起的炎症反应。然而，CD11b对小胶质细胞的功能尚不清楚。在目前的研究中，我们证明cd11b缺陷的小胶质细胞产生更多的炎症细胞因子，如白细胞介素-6和肿瘤坏死因子α，而较少的抗炎细胞因子。信号转导实验证实，核因子-κB激活在cd11b缺失的小胶质细胞中增加，这是由于Src的激活降低所致。PP1对Src的抑制显著增加了野生型小胶质细胞的炎症，但在cd11b缺乏的小胶质细胞中没有。在体内，cd11b缺陷小鼠更容易发生慢性收缩性损伤引起的异常痛觉和痛觉过敏，炎症细胞因子表达明显增加。这些结果表明，CD11b-Src信号通路对小胶质细胞炎症和抗炎细胞因子的调控功能是神经性疼痛治疗的潜在靶点。
Neuroinflammation plays an important role in the induction and maintenance of chronic pain. Orchestra of pattern-recognition receptor-induced pro-inflammatory and anti-inflammatory cytokines is critical for inflammation homeostasis. CD11b on macrophages could inhibit toll-like receptor (TLR) activation-induced inflammatory responses. However, the function of CD11b on microglia remains unknown. In the current study, we demonstrated that CD11b-deficient microglia cells produced more inflammatory cytokines, such as interleukin-6 and tumor necrosis factor alpha, while less anti-inflammatory cytokines. Signal transduction assay confirmed that nuclear factor-κB activation was increased in CD11b-deficient microglia cells, which resulted from decreased activation of Src. Inhibition of Src by PP1 increased inflammation in wild-type microglia cells significantly, but not in CD11b-deficient microglia cells. In vivo, CD11b-deficient mice were more susceptible to chronic constrictive injury-induced allodynia and hyperalgesia with significantly more inflammatory cytokines expression. All these results indicated that the regulatory function of CD11b-Src signal pathway on both inflammatory and anti-inflammatory cytokines in microglia cells is a potential target in neuropathic pain treatment.
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影响因子：
30.5
作者：
Hamerman, JA;Tchao, NK;Lanier, LL
通讯作者：
Lanier, LL
影响因子：
7.4
作者：
Osikowicz, Maria;Mika, Joanna;Przewlocka, Barbara
通讯作者：
Przewlocka, Barbara
影响因子：
13.9
作者：
Costigan M;Scholz J;Woolf CJ
通讯作者：
Woolf CJ
影响因子：
5.4
作者：
Li, Qian;Guo, Zhenhong;Cao, Xuetao
通讯作者：
Cao, Xuetao
DOI：
10.1038/nri1957
发表时间：
2006-11
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
Marshak-Rothstein A
通讯作者：
Marshak-Rothstein A