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Proteasome inhibitor-induced cyclooxygenase-2 expression in Raw264.7 cells is potentiated by inhibition of c-Jun N-terminal kinase activation

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Author(s)
박종욱권택규
Alternative Author(s)
Park, Jong WookKwon, Taeg Kyu
Publication Year
2006
Abstract
Prostaglandins play regulatory roles in a variety of physiological and pathological processes in immune response and inflammation. MG132, proteasome inhibitor, is known to anti-tumor agent activity and anti-inflammation with inhibitory property of NF-κB. We investigated the effect of MG132 on the expression of cyclooxygenase-2 (COX-2), the rate-limiting enzyme in the synthesis of PGE2, using macrophage cell line, Raw264.7. Our results showed that COX-2 expression is up-regulated by MG132 treatment and that this induction of COX-2 is regulated in part at the transcriptional level. In addition, we demonstrated the signal transduction pathway of mitogen-activated protein kinase (MAP kinase) in MG132-induced COX-2 expression. The p38 MAPK inhibitor (SB 203580) prevented MG132-induced COX-2 expression, whereas c-Jun N-terminal kinase (JNK) inhibitor (SP 600125) and MAPK kinase 4 (MKK4)-DN (dominant negative mutant) and MKK7-DN significantly enhanced COX-2 expression. These results suggest that MG132-induced COX-2 expression is associated with the activation of p38 MAPK and the inhibition of JNK signaling pathways.

Keywords
Proteasome inhibitor;
MG132;
COX-2;
JNK;
COX-2 promoter
Department
Dept. of Immunology (면역학)
Publisher
School of Medicine
Citation
Biochemical and Biophysical Research Communications, Vol.342(4) : 1334-1340, 2006
Type
Article
ISSN
0006-291X
DOI
10.1016/j.bbrc.2006.02.105
URI
http://kumel.medlib.dsmc.or.kr/handle/2015.oak/35168
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