Involvement of PKCα/β in TLR4 and TLR2 dependent activation of NF-κB

被引:103
作者
Asehnoune, K
Strassheim, D
Mitra, S
Kim, JY
Abraham, E
机构
[1] Univ Colorado, Hlth Sci Ctr, Div Pulm Sci & Crit Care Med, Denver, CO 80262 USA
[2] Hop Bicetre, UPRES EA 3540, Serv Anesthesie Reanimat, Le Kremlin Bicetre, France
[3] Hop Bicetre, UPRES EA 3540, Unite Propre Rech Enseignement Super Equipe Accue, Le Kremlin Bicetre, France
关键词
PKC; neutrophils; NF-kappa B; TLR; cell signalling; kinases;
D O I
10.1016/j.cellsig.2004.08.005
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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.
引用
收藏
页码:385 / 394
页数:10
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