Verotoxin activates mitogen-activated protein kinase in human peripheral blood monocytes: role in apoptosis and proinflammatory cytokine release
Verotoxin activates mitogen-activated protein kinase in human peripheral blood monocytes: role in apoptosis and proinflammatory cytokine release
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DOI：
10.1038/sj.bjp.0705560
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发表时间：
2003-12-01
影响因子：
7.3
通讯作者：
Plevin, R
中科院分区：
文献类型：
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作者：
Cameron, P;Smith, SJ;Plevin, R
在这项研究中，我们研究了丝裂原活化蛋白（MAP）激酶在大肠杆菌O157:H7毒毒素（VTs）对人类单核细胞凋亡和肿瘤坏死因子α (tnf - α)和粒细胞-巨噬细胞集落刺激因子（GM-CSF）释放的影响中的作用VT1和VT2均能刺激单核细胞c- jun - n末端激酶（JNK）活性的微弱、短暂性增加，以及p38分裂原活化蛋白激酶（MAP激酶）和细胞外调节激酶（ERK）活性的强烈激活，这种情况在p38 MAP激酶的情况下持续存在用VT2刺激人单核细胞（100 ng ml(-1)）未导致细胞凋亡增加；然而，毒素刺激了tnf - α和gm - csf的释放p38 MAP激酶抑制剂SB203580预处理人单核细胞，浓度从100 nM到10 muM，显著降低VT1-和vt2诱导的tnf - α和GM-CSF释放。相比之下，PD98059抑制MEK1仅能显著降低GM-CSF的释放SP600125预处理单核细胞可抑制GM-CSF和tnf - α的产生；然而，对p38 MAP激酶和ERK活化有显著影响综上所述，这些结果表明p38 MAP激酶和ERK在对verotoxins的反应中产生细胞因子的作用。JNK的角色仍未确定。
1 In this study, we examined the role of mitogen-activated protein (MAP) kinases in the effects of verotoxins (VTs), from Eycherichia coli O157:H7, upon both apoptosis and the release of tumour necrosis factor alpha (TNF-alpha) and granulocyte-macrophage colony-stimulated factor (GM-CSF) from human monocytes.2 Both VT1 and VT2 stimulated a weak, transient increase in c-Jun-N-terminal kinase (JNK) activity and a strong activation of both p38 mitogen-activated protein kinase (MAP kinase) and extracellular-regulated kinase (ERK) activity in human monocytes, which was sustained in the case of p38 MAP kinase.3 Stimulation of human monocytes with VT2 (100 ng ml(-1)) did not result in an increase in apoptosis; however, the toxin stimulated the release of both TNF-alpha and GM-CSF.4 Pretreatment of human monocytes with the p38 MAP kinase inhibitor SB203580, at concentrations from 100 nM to 10 muM, significantly decreased the VT1- and VT2-induced TNF-alpha and GM-CSF release from monocytes. In contrast, inhibition of MEK1 with PD98059 only significantly decreased GM-CSF release.5 Pretreatment of monocytes with SP600125 inhibited both GM-CSF and TNF-alpha production; however, significant effects upon p38 MAP kinase and ERK activation were observed.6 Taken together, these results suggest a role for p38 MAP kinase and ERK in cytokine generation in response to the verotoxins. A role for JNK remains undetermined.