Involvement of PKCα/β in TLR4 and TLR2 dependent activation of NF-κB
Involvement of PKCα/β in TLR4 and TLR2 dependent activation of NF-κB
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DOI：
10.1016/j.cellsig.2004.08.005
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发表时间：
2005-03-01
影响因子：
4.8
通讯作者：
Abraham, E
中科院分区：
文献类型：
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作者：
Asehnoune, K;Strassheim, D;Abraham, E
在脂多糖或前列腺素刺激的中性粒细胞中，研究了TLR4或TLR2下游依赖的蛋白激酶C(PKC)α/β信号转导事件。用结构不同的PKCalpha/β抑制剂Go6976或GF109203X预处理中性粒细胞可减少核因子-kappaB的核转位和促炎细胞因子TNF-α的产生。抑制PKCalpha/β还可阻止内毒素或PGN诱导的IKKalpha/β的磷酸化、IkappaB-α的磷酸化和降解，以及NF-kappaB p65亚单位的磷酸化。在PKCalpha/β被抑制的中性粒细胞中，p38、JNK和ERK 1/2对TLR2结合的反应被减弱。然而，当PKCalpha/β被阻断时，在TLR4刺激的中性粒细胞中，这些激酶的激活没有变化。这些结果表明，TLR4和TLR2刺激诱导了导致MAPK激活的不同的细胞内信号通路。PKCalpha/β可以通过促进核转录因子-kappaB的核转位和刺激p65亚基的磷酸化来调节中性粒细胞中依赖于核因子-kappaB的转录。(C)2004 Elsevier Inc.保留所有权利。
Protein kinase C (PKC)alpha/beta dependent signaling events downstream of TLR4 or TLR2 were investigated in neutrophils stimulated with LPS or PGN. Pretreatment of neutrophils with the structurally distinct PKCalpha/beta inhibitors Go6976 or GF109203X decreased nuclear translocation of NF-kappaB and production of the proinflammatory cytokine TNF-alpha. Inhibition of PKCalpha/beta also prevented LPS or PGN induced phosphorylation of IKKalpha/beta, phosphorylation and degradation of IkappaB-alpha, as well as phosphorylation of the p65 subunit of NF-kappaB. Activation of p38, JNK, and ERK 1/2 in response to TLR2 engagement was diminished in neutrophils in which PKCalpha/beta was inhibited. However, no alteration in the activation of these kinases was found in TLR4 stimulated neutrophils when PKCalpha/beta was blocked. Such results indicate that distinct intracellular signalling pathways leading to MAPK activation are induced by TLR4 and TLR2 stimulation. PKCalpha/beta can regulate NF-kappaB dependent transcription in neutrophils both by enhancing nuclear translocation of NF-kappaB and also by stimulating phosphorylation of the p65 subunit. (C) 2004 Elsevier Inc. All rights reserved.