NF-kappaB, but not p38 MAP kinase, is required for TNF-alpha-induced expression of cell adhesion molecules in endothelial cells.
NF-kappaB, but not p38 MAP kinase, is required for TNF-alpha-induced expression of cell adhesion molecules in endothelial cells.
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DOI：
10.1002/jcb.21845
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发表时间：
2008-10-01
影响因子：
4
通讯作者：
Guo, Yan-Lin
中科院分区：
文献类型：
--
作者：
Rajan, Suja;Ye, Jianiming;Bai, Shashan;Huang, Faqing;Guo, Yan-Lin
In response to inflammation stimuli, tumor necrosis factor-α (TNF-α) induces expression of cell adhesion molecules (CAMs) in endothelial cells (ECs). Studies have suggested that the nuclear factor-κB (NF-κB) and the p38 MAP kinase (p38) signaling pathways play central roles in this process, but conflicting results have been reported. The objective of this study is to determine the relative contributions of the two pathways to the effect of TNF-α. Our initial data indicated that blockade of p38 activity by chemical inhibitor SB203580 (SB) at 10 μM moderately inhibited TNF-α-induced expression of three types of CAMs; ICAM-1, VCAM-1 and E-selectin, indicating that p38 may be involved in the process. However, subsequent analysis revealed that neither 1 μM SB that could completely inhibit p38 nor specific knockdown of p38α and p38β with small interference RNA (siRNA) had an apparent effect, indicating that p38 activity is not essential for TNF-α-induced CAMs. The most definitive evidence to support this conclusion was from the experiments using cells differentiated from p38α knockout embryonic stem cells. We could show that deletion of p38α gene did not affect TNF-α–induced ICAM-1 and VCAM-1 expression when compared with wild type cells. We further demonstrated that inhibition of NF-κB completely blocked TNF-α-induced expression of ICAM-1, VCAM-1 and E-selectin. Taken together, our results clearly demonstrate that NF-κB, but not p38, is critical for TNF-α-induced CAM expression. The inhibition of SB at 10 μM on TNF-α-induced ICAM-1, VCAM-1 and E-selectin is likely due to the nonspecific effect of SB.
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DOI：
10.1111/j.1432-1033.2004.03982.x
发表时间：
2004-02-01
期刊：
EUROPEAN JOURNAL OF BIOCHEMISTRY
影响因子：
--
作者：
Holden, NS;Catley, MC;Newton, R
通讯作者：
Newton, R
影响因子：
6.1
作者：
Jiang, MZ;Tsukahara, H;Mayumi, M
通讯作者：
Mayumi, M
影响因子：
2.5
作者：
Guo, Yan-Lin;Ye, Jianming;Huang, Faqing
通讯作者：
Huang, Faqing
影响因子：
20.3
作者：
Goebeler, M;Kilian, K;Ludwig, S
通讯作者：
Ludwig, S
DOI：
10.1124/jpet.103.057422
发表时间：
2003-12-01
影响因子：
3.5
作者：
Ju, HS;Behm, DJ;Willette, RN
通讯作者：
Willette, RN