Role of CLIC4 in the host innate responses to bacterial lipopolysaccharide.
Role of CLIC4 in the host innate responses to bacterial lipopolysaccharide.
复制标题
DOI：
10.1002/eji.201041266
复制
发表时间：
2011-05
影响因子：
5.4
通讯作者：
Ding, Aihao
中科院分区：
文献类型：
--
作者：
He, Guoan;Ma, Yao;Chou, Szu-Yi;Li, Huihong;Yang, Chingwen;Chuang, Jen-Zen;Sung, Ching-Hwa;Ding, Aihao
氯离子细胞内通道（CLIC）4在膜运输、细胞凋亡、血管生成和细胞分化中具有多种功能。CLIC4在巨噬细胞中大量表达，但其在天然免疫功能中的作用尚不清楚。在此我们表明，原代小鼠巨噬细胞在接触细菌脂多糖（LPS）后，CLIC4的表达量增加。给小鼠注射LPS后，其脑、心、肺、肾、肝和脾中的内源性CLIC4水平显著升高。稳定的过表达CLIC4的巨噬细胞系在接触LPS时，比模拟转染细胞产生更多的肿瘤坏死因子（TNF）、白细胞介素 - 6（IL - 6）、白细胞介素 - 12（IL - 12）和趋化因子（CCL5）。为了探究CLIC4在体内的作用，我们培育了CLIC4缺失小鼠。这些小鼠免受LPS诱导的死亡，其血清炎症细胞因子水平降低。在感染单核细胞增生李斯特菌时，CLIC4缺陷小鼠清除感染的能力受损，并且其巨噬细胞对李斯特菌的反应是产生比野生型对照更少的炎症细胞因子和趋化因子。当在体外受到LPS刺激时，CLIC4基因的缺失对丝裂原活化蛋白激酶（MAPK）和核因子 - κB（NF - κB）的激活影响较小，但导致巨噬细胞内磷酸化干扰素调节因子3（IRF3）的积累减少。相反，CLIC4的过表达增强了LPS介导的IRF3。因此，CLIC4是一种LPS诱导产物，可作为LPS信号传导的正调节因子。
Chloride intracellular channel (CLIC) 4 has diverse functions in membrane trafficking, apoptosis, angiogenesis and cell differentiation. CLIC4 is abundantly expressed in macrophages, but its role in innate immune functions is unclear. Here we show that primary murine macrophages expressed increased amounts of CLIC4 after exposure to bacterial lipopolysaccharide (LPS). The endogenous CLIC4 level is significantly elevated in the brain, heart, lung, kidney, liver and spleen after LPS injection of mice. Stable macrophage lines overexpressing CLIC4 produced more TNF, IL-6, IL-12 and CCL5 than mock transfectants when exposed to LPS. To explore the role of CLIC4 in vivo, we generated CLIC4-null mice. These mice were protected from LPS-induced death, had reduced serum levels of inflammatory cytokines. Upon infection with Listeria monocytogenes, CLIC4-deficient mice were impaired in their ability to clear infection, and their macrophages responded to Listeria by producing less inflammatory cytokines and chemokines than the wild type controls. When challenged with LPS in vitro, deletion of clic4 gene had little effect in MAPK and NF-κB activation, but led to a reduced accumulation of phosphorylated IRF3 within macrophages. Conversely, overexpression of CLIC4 enhanced LPS-mediated IRF3. Thus, CLIC4 is an LPS-induced product that can serve as a positive regulator of LPS signaling.
登录
查看更多内容
DOI：
10.1152/ajprenal.1999.276.3.f398
发表时间：
1999-03-01
影响因子：
4.2
作者：
Edwards, JC
通讯作者：
Edwards, JC
影响因子：
4.4
作者：
Jefferies, CA;O'Neill, LAJ
通讯作者：
O'Neill, LAJ
影响因子：
4.4
作者：
Martinez, Fernando O.;Gordon, Siamon;Mantovani, Alberto
通讯作者：
Mantovani, Alberto
影响因子：
4.8
作者：
Harrop, SJ;DeMaere, MZ;Curmi, PMG
通讯作者：
Curmi, PMG
影响因子：
5
作者：
Andersen, J.;VanScoy, S.;Reich, N. C.
通讯作者：
Reich, N. C.