FIBRONECTIN-MEDIATED CELL-ADHESION IS REQUIRED FOR INDUCTION OF 92-KDA TYPE-IV COLLAGENASE GELATINASE (MMP-9) GENE-EXPRESSION DURING MACROPHAGE DIFFERENTIATION - THE SIGNALING ROLE OF PROTEIN-KINASE C-BETA/

Citation
B. Xie et al., FIBRONECTIN-MEDIATED CELL-ADHESION IS REQUIRED FOR INDUCTION OF 92-KDA TYPE-IV COLLAGENASE GELATINASE (MMP-9) GENE-EXPRESSION DURING MACROPHAGE DIFFERENTIATION - THE SIGNALING ROLE OF PROTEIN-KINASE C-BETA/, The Journal of biological chemistry, 273(19), 1998, pp. 11576-11582
Citations number
58
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Biology
ISSN journal
0021-9258
Volume
273
Issue
19
Year of publication
1998
Pages
11576 - 11582
Database
ISI
SICI code
0021-9258(1998)273:19<11576:FCIRFI>2.0.ZU;2-Q
Abstract
Induction of the 92-kDa gelatinase (MMP-9) gene expression is associat ed with macrophage differentiation. In this study, we explored the reg ulatory mechanisms underlying this differentiation-associated MMP-9 ge ne expression in human HL-60 myeloid leukemia cells and human peripher al blood monocytes. Phorbol 12-myristate 13-acetate (PMA) markedly ind uced MMP-9 gene expression in HL-60 cells; the induction closely paral leled the timing and extent of PMA-induced cell adhesion and spreading , a hallmark of macrophage differentiation. Similarly, treatment with PMA or macrophage-colony stimulating factor stimulated adherence and s preading of blood monocytes with a concurrent 7- or 5-fold increase in MMP-9 production, respectively. In protein kinase C (PRC)-beta-defici ent HL-60 variant cells (HL-525), PMA failed to induce cell adhesion a nd MMP-9 gene expression. Transfecting HL-525 cells with a PKC-beta ex pression plasmid restored PKC-beta levels and PMA inducibility of cell adhesion and spreading as well as MMP-9 gene expression. Induction of cell adhesion and MMP-9 gene expression in HL-60 cells and blood mono cytes was strongly inhibited by neutralizing monoclonal antibodies to fibronectin (FN) and its receptor alpha(5) beta(1) integrin. HL-525 ce lls, which constitutively display high levels of surface alpha(5) beta (1) integrin, adhered and spread on immobilized FN with concomitant in duction of MMP-9 gene expression. Cytochalasins B and D were each a po tent inhibitor of MMP-9 production. Our results suggest that alpha(5) beta(1) integrin-mediated interaction of immature hematopoietic cells with FN plays a critical role in modulating matrix-degrading activitie s during macrophage differentiation.