TNFα and IL-1β are mediated by both TLR4 and Nod1 pathways in the cultured HAPI cells stimulated by LPS.
TNFα and IL-1β are mediated by both TLR4 and Nod1 pathways in the cultured HAPI cells stimulated by LPS.
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DOI：
10.1016/j.bbrc.2012.03.068
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发表时间：
2012-04-20
影响因子：
3.1
通讯作者：
Hao S
中科院分区：
文献类型：
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作者：
Zheng W;Zheng X;Liu S;Ouyang H;Levitt RC;Candiotti KA;Hao S
最近越来越多的证据表明，神经胶质细胞的激活在几种神经退行性疾病和神经病理性疼痛中发挥着重要作用。中枢神经系统中的小胶质细胞表达Toll样受体4(TLR4)，TLR4被认为是脂多糖(LPS)的主要受体。脂多糖激活TLR4信号通路，诱导促炎分子的产生。在目前的研究中，我们使用培养的高侵袭性增殖永生化(HAPI)小胶质细胞来验证内毒素信号通路。结果发现，HAPI细胞经脂多糖处理后，TLR4、磷酸化JNK、磷酸化核因子κB、肿瘤坏死因子α和IL-1β的表达均上调。用siRNA沉默TLR4可降低pJNK、肿瘤坏死因子α和IL-1β的表达，但不影响pNF-κB的表达。用JNK抑制剂SP600125抑制JNK可降低肿瘤坏死因子α和IL-1β的表达。出乎意料的是，我们发现用ML130抑制Nod1显著降低了pNF-κB的表达。抑制NF-κB也降低了肿瘤坏死因子α和IL-1β的表达。Nod1配体dap诱导pNF-κB表达上调，该作用可被Nod1抑制剂阻断。这些结果表明，内毒素诱导的pJNK是TLR4依赖的，而pNF-κB是内毒素诱导的Hapi细胞中Nod1依赖的。TLR4-JNK或Nod1-NF-κB途径参与了肿瘤坏死因子α和IL-1β的表达。
A growing body of evidence recently suggests that glial cell activation plays an important role in several neurodegenerative diseases and neuropathic pain. Microglia in the central nervous system express toll-like receptor 4 (TLR4) that is traditionally accepted as the primary receptor of lipopolysaccharide (LPS). LPS activates TLR4 signaling pathways to induce the production of proinflammatory molecules. In the present studies, we verified the LPS signaling pathways using cultured highly aggressively proliferating immortalized (HAPI) microglial cells. We found that HAPI cells treated with LPS upregulated the expression of TLR4, phospho-JNK (pJNK) and phospho-NF-κB (pNF-κB), TNFα and IL-1β. Silencing TLR4 with siRNA reduced the expression of pJNK, TNFα and IL-1β, but not pNF-κB in the cells. Inhibition of JNK with SP600125 (a JNK inhibitor) decreased the expression of TNFα and IL-1β. Unexpectedly, we found that inhibition of Nod1 with ML130 significantly reduced the expression of pNF-κB. Inhibition of NF-κB also reduced the expression of TNFα and IL-1β. Nod1 ligand, DAP induced the upregulation of pNF-κB which was blocked by Nod1 inhibitor. These data indicate that LPS-induced pJNK is TLR4-dependent, and that pNF-κB is Nod1-dependent in HAPI cells treated with LPS. Either TLR4-JNK or Nod1-NF-κB pathways is involved in the expression of TNFα and IL-1β.
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影响因子：
--
作者：
Correa RG;Khan PM;Askari N;Zhai D;Gerlic M;Brown B;Magnuson G;Spreafico R;Albani S;Sergienko E;Diaz PW;Roth GP;Reed JC
通讯作者：
Reed JC
影响因子：
2.3
作者：
Poltorak, A;Smirnova, I;Beutler, B
通讯作者：
Beutler, B
影响因子：
6.2
作者：
Qin, LY;Li, GR;Block, ML
通讯作者：
Block, ML
影响因子：
6.2
作者：
Gorina, Roser;Font-Nieves, Miriam;Planas, Anna M.
通讯作者：
Planas, Anna M.
TLR信号传导和内毒素耐受性中的microRNA。
影响因子：
24.1
作者：
通讯作者：
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