Thalidomide destabilizes cyclooxygenase-2 mRNA by inhibiting p38 mitogen-activated protein kinase and cytoplasmic shuttling of HuR

被引：30

作者：

Jin, Soo Hyun

Kim, Tae Il

Yang, Kyoung Min

Kim, Won Ho

机构：

[1] Yonsei Univ, Coll Med, Dept Internal Med, Seoul 120752, South Korea

[2] Yonsei Univ, Coll Med, Inst Gastroenterol, Brain Korea 21 Project Med Sci, Seoul 120752, South Korea

来源：

EUROPEAN JOURNAL OF PHARMACOLOGY | 2007年 / 558卷 / 1-3期

关键词：

thalidomide; cyclooxygenase-2; p38 MAPK (p38 mitogen-activated protein kinase); HuR (Hu antigen R); mRNA stability;

D O I：

10.1016/j.ejphar.2006.11.060

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

We investigated the effect of thalidomide on transcriptional and post-transcriptional cyclooxygenase-2 (COX-2) expression, including a pathway leading to COX-2 mRNA destabilization. We found that thalidomide inhibited the interleukin-1 beta (IL-1 beta)-mediated induction of COX-2 protein and mRNA in Caco-2 cells. Transient transfection with a COX-2 promoter construct demonstrated that thalidomide did not affect IL-1 beta-induced transcriptional activation of COX-2, although it did decrease the stability of COX-2 mRNA and suppress IL-1 beta-induced cytoplasmic shuttling of an mRNA stabilizing protein, HuR. Thalidomide also suppressed IL-1 beta-induced p38 mitogen-activated protein kinase (MAPK) activation, while a p38 MAPK inhibitor destabilized COX-2 mRNA and the cytoplasmic shuttling of HuR induced by IL-1 beta. These data suggest that one of the molecular mechanisms of thalidomide may be destabilization of COX-2 mRNA through inhibition of cytoplasmic shuttling of HuR and p38 MAPK. (c) 2006 Elsevier B.V. All rights reserved.

引用

页码：14 / 20

页数：7

共 58 条

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