The identification of C/EBPβ as a transcription factor necessary for the induction of MAPK phosphatase-1 by toll-like receptor-4 ligand
The identification of C/EBPβ as a transcription factor necessary for the induction of MAPK phosphatase-1 by toll-like receptor-4 ligand
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DOI：
10.1016/j.abb.2008.08.007
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发表时间：
2008-11-01
影响因子：
3.9
通讯作者：
Kim, Sang Geon
中科院分区：
文献类型：
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作者：
Cho, Il Je;Woo, Na Ri;Kim, Sang Geon
Toll样受体激活促分裂原活化蛋白激酶（MAPK），其有助于炎症反应。MAPK的活性由MAPK磷酸酶（MKP）平衡。由于mkp-1的转录调控机制尚未完全建立，因此本研究研究了Toll样受体-4配体（TLR 4L，脂多糖）对Raw 264.7细胞中CCAAT/增强子结合蛋白-β（C/EBP β）依赖性诱导MKP-1的影响。TLR 4L处理通过基因转录诱导MKP-1。其他TLRL也反式激活mkp-1。凝胶位移、免疫印迹和染色质免疫沉淀分析鉴定了TLR 4L对C/EBP β的激活作用。同样，C/EBP β转染促进mkp-1的反式激活，这被其显性负突变体（AC/EBP）逆转。使用化学抑制剂或MAPKs显性失活突变体的实验表明，C/ EBP β激活和MKP-1诱导都依赖于MAPKs的激活。C/EBP β的TLR 4L活化也有助于dusp-2、dusp-4、dusp-8和dusp-16的诱导。这些结果将C/EBP β鉴定为TLRL诱导MKP-1所必需的转录因子。(c)2008年爱思唯尔公司All rights reserved.
Toll-like receptor activates mitogen-activated protein kinases (MAPKs), which contributes to inflammatory responses. The activities of MAPKs are counter-balanced by MAPK phosphatases (MKPs). Because the transcriptional regulatory mechanism of mkp-1 has not been completely established, this study investigated the effect of toll-like receptor-4 ligand (TLR4L, lipopolysaccharide) on CCAAT/enhancer binding protein-beta (C/EBP beta)-dependent induction of MKP-1 in Raw264.7 cells. TLR4L treatment induced MKP-1 through gene transcription. Other TLRLs also transactivated mkp-1. Gel-shift, immunoblot and chromatin immunoprecipitation assays identified the activation of C/EBP beta by TLR4L. Consistently, C/EBP beta transfection promoted mkp-1 transactivation, which was reversed by its dominant-negative mutant (AC/EBP). Experiments using chemical inhibitors or dominant-negative mutants of MAPKs indicated that both C/ EBP beta activation and MKP-1 induction depend on the activation of MAPKs. TLR4L activation of C/EBP beta also contributed to the induction of dusp-2, dusp-4, dusp-8 and dusp-16. These results identify C/EBP beta as a transcription factor necessary for the induction of MKP-1 by TLRL. (c) 2008 Elsevier Inc. All rights reserved.