Chylomicron remnants upregulate CD40 expression via the ERK pathway and a redox-sensitive mechanism in THP-1 cells
Chylomicron remnants upregulate CD40 expression via the ERK pathway and a redox-sensitive mechanism in THP-1 cells
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DOI：
10.1016/j.atherosclerosis.2005.09.002
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发表时间：
2006-08-01
期刊：
影响因子：
5.3
通讯作者：
Yokoyama, Mitsuhiro
中科院分区：
文献类型：
--
作者：
Kamemura, Kohei;Fujioka, Yoshio;Yokoyama, Mitsuhiro
CD 40是一种48 kDa的磷酸化跨膜糖蛋白，属于肿瘤坏死因子受体超家族，可能在动脉粥样硬化斑块的形成中发挥作用。在这里，我们研究了乳糜微粒残留对人前单核细胞系THP-1细胞中CD 40表达的影响。乳糜微粒残余物以剂量和时间依赖性方式上调CD 40蛋白和mRNA的表达。此外，乳糜微粒残余物增加了活性氧物质的产生，如通过增加的2 '，7'-二氯荧光素水平所确定的。预处理的抗氧化剂，N-乙酰半胱氨酸，抑制乳糜微粒残基诱导的CD 40蛋白表达的60%。另一方面，乳糜微粒残留物瞬时增加细胞外信号调节激酶（ERK 1/2）和p38丝裂原活化蛋白激酶（MAPK）的磷酸化。用MAPK激酶抑制剂U 0126预处理，完全抑制乳糜微粒残体诱导的CD 40蛋白表达，而p38 MAPK抑制剂SB 203580则没有影响。N-乙酰半胱氨酸预处理对乳糜微粒残基诱导的ERK 1/2磷酸化无影响。提示乳糜微粒刺激THP-1细胞表达CD 40依赖于ERK 1/2介导的信号通路，之后是氧化还原敏感机制依赖和非依赖的信号通路。因此，乳糜微粒残余物可能通过其免疫和促炎作用促进动脉粥样硬化斑块的形成。(c)2005爱思唯尔爱尔兰有限公司保留所有权利。
CD40 is a 48 kDa phosphorylated transmembrane glycoprotein that belongs to the tumor necrosis factor receptor superfamily and may play a role in formation of atherosclerotic plaques. Here, we investigated the effect of chylomicron remnants on CD40 expression in the human premonocytic cell line, THP-1 cells. Chylomicron remnants upregulated the expression of CD40 protein and mRNA in a dose- and time-dependent manner. Further, chylomicron remnants increased the generation of reactive oxygen species as determined by an increasing level of 2',7'-dichlorofluorescein. Pretreatment with the antioxidant, N-acetylcysteine, inhibited chylomicron remnant-induced CD40 protein expression by 60%. On the other hand, chylomicron remnants transiently increased the phosphorylation of extracellular signal-regulated kinase (ERK 1/2) and p38 mitogen-activated protein kinase (MAPK). Pretreatment with the MAPK kinase inhibitor, U0126, completely inhibited chylomicron remnants-induced CD40 protein expression, whereas the p38 MAPK inhibitor, SB203580, had no effect. Pretreatment with N-acetylcysteine had no effect on chylomicron remnant-induced ERK 1/2 phosphorylation. These data suggest that CD40 expression stimulated by chylomicron remnants in THP-1 cells is dependent on ERK 1/2-mediated pathway, which is followed by redox-sensitive mechanism-dependent and independent pathway. Thus, chylomicron remnants may contribute to the formation of atherosclerotic plaques via their immunological and proinflammatory effects. (c) 2005 Elsevier Ireland Ltd. All rights reserved.