Src kinase participates in LPS-induced activation of NADPH oxidase.
Src kinase participates in LPS-induced activation of NADPH oxidase.
复制标题
DOI：
10.1016/j.molimm.2009.10.012
复制
发表时间：
2010-01
影响因子：
3.6
通讯作者：
Wheeler, Michael D.
中科院分区：
文献类型：
--
作者：
Check, Jennifer;Byrd, Christy L.;Menio, Jade;Rippe, Richard A.;Hines, Ian N.;Wheeler, Michael D.
巨噬细胞对内毒素（LPS）的反应产生NADPH氧化酶的超氧化物是一种重要的先天免疫反应，但目前尚不清楚LPS是如何激活NADPH氧化酶的。假设lps诱导的src激酶和PI3K激酶（PI3K）促进了NADPH氧化酶的调控亚基p47phox的激活。在小鼠巨噬细胞RAW264.7细胞中，抑制src酪氨酸家族激酶可抑制lps诱导的NADPH氧化酶激活、p47phox磷酸化、PI3K激活和TLR4磷酸化。此外，抑制lps诱导的细胞内钙的增加减弱了src激酶的激活、PI3K与TLR4的关联以及PI3激酶的激活。这些数据表明src激酶和PI3激酶都参与了lps诱导的NADPH氧化酶活化。重要的是，这些数据表明，lps诱导的src激酶激活对于PI3激酶激活和TLR4磷酸化至关重要，并且依赖于lps诱导的细胞内钙的增加。这些信号事件填补了我们对脂多糖诱导的自由基产生的理解的关键空白，并可能潜在地负责类固醇或乙醇引起的先天免疫耐受或脱敏的机制。
The production of superoxide from NADPH oxidase by macrophages in response to endotoxin (LPS) is an important innate immune response, yet it is not clear how LPS signals the activation of NADPH oxidase. The hypothesis is that LPS-induced src kinase and PI3 kinase (PI3K) facilitates the activation of p47phox, the regulatory subunit of NADPH oxidase. In mouse macrophage RAW264.7 cells, inhibition of src tyrosine family kinases inhibited LPS-induced activation of NADPH oxidase, phosphorylation of p47phox, activation of PI3K and phosphorylation of the TLR4. Moreover, inhibition of LPS-induced increases in intracellular calcium blunted src kinase activation, PI3K association with TLR4, as well as PI3 kinase activation. These data suggest that both src kinase and PI3 kinase are involved in LPS-induced NADPH oxidase activation. Importantly, these data suggest that LPS-induced src kinase activation is critical for PI3 kinase activation as well as TLR4 phosphorylation and is dependent upon LPS-induced increase in intracellular calcium. These signaling events fill critical gaps in our understanding of LPS-induced free radical production as well as may potentially responsible for the mechanism of innate immune tolerance or desensitization caused by steroids or ethanol.
登录
查看更多内容
DOI：
10.1161/01.atv.0000143096.15099.ce
发表时间：
2004-10-01
影响因子：
8.7
作者：
Schabbauer, G;Tencati, M;Mackman, N
通讯作者：
Mackman, N
影响因子：
16.8
作者：
Fukao, T;Koyasu, S
通讯作者：
Koyasu, S
影响因子：
4.8
作者：
Medvedev, Andrei E.;Piao, Wenji;Vogel, Stefanie N.
通讯作者：
Vogel, Stefanie N.
影响因子：
3.1
作者：
Li, XW;Tupper, JC;Harlan, JM
通讯作者：
Harlan, JM
影响因子：
3.1
作者：
Orlicek, SL;Hanke, JH;English, BK
通讯作者：
English, BK