TNF-alpha induction by LPS is regulated posttranscriptionally via a Tpl2/ERK-dependent pathway.
TNF-alpha induction by LPS is regulated posttranscriptionally via a Tpl2/ERK-dependent pathway.
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发表时间：
2000
期刊：
影响因子：
64.5
通讯作者：
C. Dumitru;J. Ceci;C. Tsatsanis;D. Kontoyiannis;K. Stamatakis;J. Lin;C. Patriotis;N. Jenkins;
中科院分区：
文献类型：
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作者：
C. Dumitru;J. Ceci;C. Tsatsanis;D. Kontoyiannis;K. Stamatakis;J. Lin;C. Patriotis;N. Jenkins;
当暴露于脂多糖（LPS）时，Tpl2敲除小鼠产生低水平的tnf - α，并且它们对LPS/ d -半乳糖胺诱导的病理具有抗性。LPS刺激这些小鼠的腹腔巨噬细胞不激活MEK1、ERK1和ERK2，但激活JNK、p38 MAPK和NF-kappaB。ERK1和ERK2激活的阻断与tnf - α诱导的缺陷有因果关系，实验表明，用MEK抑制剂PD98059处理的正常小鼠巨噬细胞也表现出类似的缺陷。删除tnf - α mRNA中富含au的基序可以最小化Tpl2失活对tnf - α诱导的影响。LPS刺激的巨噬细胞亚细胞分离显示，Tpl2转导的LPS信号特异性地促进了tnf - α mRNA从细胞核向细胞质的转运。
Tpl2 knockout mice produce low levels of TNF-alpha when exposed to lipopolysaccharide (LPS) and they are resistant to LPS/D-Galactosamine-induced pathology. LPS stimulation of peritoneal macrophages from these mice did not activate MEK1, ERK1, and ERK2 but did activate JNK, p38 MAPK, and NF-kappaB. The block in ERK1 and ERK2 activation was causally linked to the defect in TNF-alpha induction by experiments showing that normal murine macrophages treated with the MEK inhibitor PD98059 exhibit a similar defect. Deletion of the AU-rich motif in the TNF-alpha mRNA minimized the effect of Tpl2 inactivation on the induction of TNF-alpha. Subcellular fractionation of LPS-stimulated macrophages revealed that LPS signals transduced by Tpl2 specifically promote the transport of TNF-alpha mRNA from the nucleus to the cytoplasm.