Release of heat shock protein 70 (Hsp70) and the effects of extracellular Hsp70 on matric metalloproteinase-9 expression in human monocytic U937 cells.
- Author:
Kyoung Jin LEE
1
;
Yoo Mih KIM
;
Dae Young KIM
;
Dooil JEOUNG
;
Kyuhyung HAN
;
Seung Taek LEE
;
Yun Sil LEE
;
Kyeong Han PARK
;
Jeong Hyun PARK
;
Dae Joong KIM
;
Jang Hee HAHN
Author Information
1. Department of Anatomy and Cell Biology, College of Medicine, Kangwon National University, Chuncheon 200-701, Korea. jhahn@kangwon.ac.kr
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords:
AP-1;
gelatinase B;
HSP70 heat-shock proteins;
monocytes;
NF-kB;
transcription factor AP-1
- MeSH:
U937 Cells;
Transfection;
Transcription Factor AP-1/metabolism;
NF-kappa B/metabolism;
Matrix Metalloproteinase 9/*metabolism;
Humans;
HSP70 Heat-Shock Proteins/metabolism/*pharmacology/*secretion;
Gene Expression Regulation;
Culture Media, Conditioned/pharmacology;
Cell Movement/drug effects
- From:Experimental & Molecular Medicine
2006;38(4):364-374
- CountryRepublic of Korea
- Language:English
-
Abstract:
Heat shock protein 70 (Hsp70) release and its effects on pro-inflammatory cytokine production have been controversial. In this study, we investigated whether Hsp70 could be released from monocytes and activates matrix metalloproteinase-9 (MMP-9) gene expression. Hsp70 overexpression in human monocytic cell line U937 was found to increase PMA- induced MMP-9 expression and enhance cell motility. Hsp70 cDNA transfectants released Hsp70 protein into culture supernatants, and a part of released Hsp70 subsequently was bound to the surface of U937 cells. Addition of culture medium containing the extracelluar Hsp70 led to an increase not only in proMMP-9 secretion, but also the invasiveness of U937 cells through Matrigel or human umbilical vascular endothelial cells (HUVEC) in vitro. Immunodepletion of Hsp70 abolished its effect on MMP-9 expression. The released Hsp70 activated nuclear factor kappa B (NF-kappa B) and activating protein-1 (AP-1), which led to the activation of MMP-9 transcription. Taken together, these results suggest that extracellular Hsp70 induces the expression of MMP-9 gene through activation of NF-kappa B and AP-1.
