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

Authors
 Soo Hyun Jin  ;  Tae Il Kim  ;  Won Ho Kim  ;  Kyoung Min Yang 
Citation
 EUROPEAN JOURNAL OF PHARMACOLOGY, Vol.558(1-3) : 14-20, 2007 
Journal Title
EUROPEAN JOURNAL OF PHARMACOLOGY
ISSN
 0014-2999 
Issue Date
2007
MeSH
Antigens, Surface/metabolism* ; Caco-2 Cells ; Cyclooxygenase 2/genetics* ; Cytoplasm/metabolism* ; ELAV Proteins ; ELAV-Like Protein 1 ; Humans ; Imidazoles/pharmacology ; Interleukin-1beta/pharmacology ; Protein Transport/drug effects ; Pyridines/pharmacology ; RNA Stability/drug effects* ; RNA-Binding Proteins/metabolism* ; Thalidomide/pharmacology* ; p38 Mitogen-Activated Protein Kinases/antagonists & inhibitors*
Abstract
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-1β (IL-1β)-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-1β-induced transcriptional activation of COX-2, although it did decrease the stability of COX-2 mRNA and suppress IL-1β-induced cytoplasmic shuttling of an mRNA stabilizing protein, HuR. Thalidomide also suppressed IL-1β-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-1β. 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.
Full Text
http://www.sciencedirect.com/science/article/pii/S0014299906013240
DOI
10.1016/j.ejphar.2006.11.060
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원) > 1. Journal Papers
Yonsei Authors
Kim, Won Ho(김원호) ORCID logo https://orcid.org/0000-0002-5682-9972
Kim, Tae Il(김태일) ORCID logo https://orcid.org/0000-0003-4807-890X
Yang, Kyoung Min(양경민)
Jin, Soo Hyun(진수현)
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/96006
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