Interleukin-1beta stimulates matrix metalloproteinase-2 expression via a prostaglandin E2-dependent mechanism in human chondrocytes.
- Author:
Young Ae CHOI
1
;
Dong Jun LEE
;
Hyung Kyu LIM
;
Jae Ho JEONG
;
Jong Kyung SONN
;
Shin Sung KANG
;
Suk Hwan BAEK
Author Information
1. Department of Biochemistry and Molecular Biology, Yeungnam University, Daegu 705-035, Korea. sbaek@med.yu.ac.kr
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords:
chondrocytes;
gelatinase A;
interleukin-1;
mitogen-activated;
prostaglandin endoperoxide synthase;
prostaglandin E;
protein kinases
- MeSH:
Chondrocytes/drug effects/*enzymology/metabolism;
Dinoprostone/analysis/*metabolism;
Gelatinase A/analysis/*biosynthesis;
Humans;
Indoles/pharmacology;
Interleukin-1/*pharmacology;
Isoenzymes/antagonists & inhibitors/metabolism;
Nitrobenzenes/pharmacology;
Phosphorylation/drug effects;
Prostaglandin-Endoperoxide Synthase/metabolism;
Protein Kinase C/antagonists & inhibitors/metabolism;
Research Support, Non-U.S. Gov't;
Sulfonamides/pharmacology;
Up-Regulation;
p38 Mitogen-Activated Protein Kinases/metabolism
- From:Experimental & Molecular Medicine
2004;36(3):226-232
- CountryRepublic of Korea
- Language:English
-
Abstract:
IL-1beta is known promote cyclooxygenase-2 (COX- 2) and matrix metalloproteinase-2 (MMP-2) expression. This study focuses on the characterization of the signaling cascade associated with IL-1beta-induced matrix metalloproteinase-2 (MMP- 2) regulation in human chondrocytes. The decrease in collagen levels in the conditioned media was prevented by a broad spectrum MMP inhibitor, suggesting that IL-1beta promotes the proteolytic process leading to MMP-2 activation. IL-1beta-related MMP-2 expression was found to be dependent on prostaglandin E2 (PGE2) production. In addition, the induction of COX-2 and MMP-2 was inhibited by the pretreatment of chondrocytes with a SB203580 or Ro 31-8220, indicating the involvement of protein kinase C (PKC) or p38 mitogen-activated protein kinase (MAPK). However, there is no cross-talk between PKC and p38 MAPK in the IL-1beta-induced MMP-2 activation. Taken together, these results demonstrated that IL-1beta induces MMP-2 expression through the PGE2-dependent mechanism in human chondrocytes.
