Release of heat shock protein 70 (Hsp70) and the effects of extracellular Hsp70 on matric metalloproteinase-9 expression in human monocytic U937 cells.
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-kappaB) 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-KappaB and AP-1.
Lee
Kyoung-Jin
KJ
Department of Anatomy and Cell Biology, College of Medicine, Kangwon National University, Chuncheon 200-701, Korea.
Kim
Yoo Mih
YM
Kim
Dae Young
DY
Jeoung
Dooil
D
Han
Kyuhyung
K
Lee
Seung-Taek
ST
Lee
Yun-Sil
YS
Park
Kyeong Han
KH
Park
Jeong Hyun
JH
Kim
Dae Joong
DJ
Hahn
Jang-Hee
JH
D002465:Cell Movement / Q000187:drug effects; D017077:Culture Media, Conditioned / Q000494:pharmacology; D005786:Gene Expression Regulation; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism* / Q000494:pharmacology*; D006801:Humans; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D018808:Transcription Factor AP-1 / Q000378:metabolism; D014162:Transfection; D020298:U937 Cells
D017077:Culture Media, Conditioned; D018840:HSP70 Heat-Shock Proteins; D016328:NF-kappa B; D018808:Transcription Factor AP-1; D020780:Matrix Metalloproteinase 9