Activation of p55 tumor necrosis factor-α receptor-1 coupled to tumor necrosis factor receptor-associated factor 2 stimulates intercellular adhesion molecule-1 expression by modulating a thapsigargin-sensitive pathway in human tracheal smooth muscle cells
Activation of p55 tumor necrosis factor-α receptor-1 coupled to tumor necrosis factor receptor-associated factor 2 stimulates intercellular adhesion molecule-1 expression by modulating a thapsigargin-sensitive pathway in human tracheal smooth muscle cells
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DOI：
10.1124/mol.58.1.237
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发表时间：
2000-07-01
影响因子：
3.6
通讯作者：
Panettieri, RA
中科院分区：
文献类型：
--
作者：
Amrani, Y;Lazaar, AL;Panettieri, RA
肿瘤坏死因子-α（TNF-α）通过激活人气道平滑肌（ASM）细胞中的转录因子核因子-κ B（NF-κ B）刺激细胞间粘附分子-1（ICAM-1）的表达。本研究描述了参与的受体以及介导苦参碱诱导的NF-κ B活化和ICAM-1表达的关键下游信号传导事件。TNF α刺激1至4小时诱导人ASM细胞ICAM-1表达。这种TNF α诱导的ICAM-1的快速表达增强了T淋巴细胞与ASM细胞的粘附，这被抗ICAM-1抗体抑制。使用免疫染色，我们证明了TNF α受体TNFR 1和TNFR 2在天然人气管平滑肌上表达。用特异性激活TNFR 1的抗体htr-9处理细胞也刺激ICAM-1 mRNA和蛋白的表达。UTR-1是一种TNFR 2的阻断抗体，不影响TNF α介导的ICAM-1表达。在用NF-κ B报告质粒转染的ASM细胞中，TNF α和htr-9均增加荧光素酶活性。显性负性TNF受体相关因子2构建体的过表达，缺乏NH 2末端RING指，完全消除了TNF α和htr-9介导的NF-κ B报告活性的增加。毒胡萝卜素是一种消耗细胞内钙储存的药物，它可以抑制细胞因子介导的NF-κ B依赖性ICAM-1 mRNA转录和蛋白质表达，但对I kappa B降解没有影响。此外，用1，2-双（2-氨基苯氧基）乙烷-N，N，N '，N'-四乙酸乙酰氧基甲酯螯合胞浆钙也抑制细胞因子TNF α诱导的ICAM-1表达。这些数据表明，TNFR 1，通过TNF受体相关因子2-NF-κ B信号通路，介导TNF α诱导的ICAM-1在ASM细胞上的表达，涉及毒胡萝卜素敏感的信号通路。
Tumor necrosis factor-alpha (TNF alpha) stimulates the expression of intercellular adhesion molecule-1 (ICAM-1) by activating the transcription factor nuclear factor-kappa B (NF-kappa B) in human airway smooth muscle (ASM) cells. This study characterizes the receptor involved as well as critical downstream signaling events mediating cytokine-induced NF-kappa B activation and ICAM-1 expression. TNF alpha stimulation for 1 to 4 h induced ICAM-1 expression in human ASM cells. This rapid TNF alpha-induced ICAM-1 expression enhanced T-lymphocyte adhesion to ASM cells, which was inhibited by anti-ICAM-1 antibodies. Using immunostaining, we demonstrated that TNF alpha receptors TNFR1 and TNFR2 are expressed on native human tracheal smooth muscle. Treatment of cells with htr-9, an antibody that specifically activates TNFR1, also stimulated expression of ICAM-1 mRNA and protein. Utr-1, a blocking antibody to TNFR2, did not affect TNF alpha-mediated ICAM-1 expression. Both TNF alpha and htr-9 increased luciferase activity in ASM cells transfected with a NF-kappa B reporter plasmid. Overexpression of a dominant negative TNF receptor-associated factor 2 construct, lacking the NH2-terminal RING finger, completely abrogated both TNF alpha- and htr-9-mediated increases in NF-kappa B reporter activity. Thapsigargin, an agent that depletes intracellular calcium stores, abrogated both cytokine-mediated NF-kappa B-dependent ICAM-1 mRNA transcription and protein expression but had no effect on I kappa B degradation. In addition, chelating cytosolic calcium with 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid acetoxymethyl ester also inhibited cytokine TNF alpha-induced ICAM-1 expression. These data suggest that TNFR1, through a TNF receptor-associated factor 2-NF-kappa B signaling pathway, mediates TNF alpha-induced expression of ICAM-1 on ASM cells by involving a thapsigargin-sensitive signaling pathway.