Regulation of gelatinase B in human monocytic and endothelial cells by PECAM-1 ligation and its modulation by interferon-beta.
Platelet endothelial cell adhesion molecule-1 (PECAM-1 or CD31) and gelatinase B are coexpressed at sites of inflammation, where an intense interaction occurs between leukocytes and endothelial cells. To investigate whether a functional link exists between PECAM-1 activation and gelatinase B production, the regulatory role of PECAM-1, IFN-gamma, IFN-beta, LPS, and PMA on the production of gelatinase B (MMP-9) was studied in vitro in normal human umbilical vein endothelial cells (HUVECs), human peripheral blood mononuclear cells (PBMCs), and in a human monocytic leukemia cell line. In THP-1 cells, progelatinase B levels were slightly up-regulated by immobilized PECAM-1-specific monoclonal antibody (mAb) and soluble recombinant PECAM-1 when compared with strong induction by LPS and PMA. IFN-beta inhibited the induced and basal gelatinase B production but had no modulating effect on the expression of PECAM-1. HUVECs mainly produced progelatinase A (proMMP-2). Treatment with LPS and triggering of the endothelial cells with PECAM-1 mAb or recombinant PECAM-1 had no effect on gelatinase A or B production, whereas PMA stimulated the production of progelatinase B. IFN-beta significantly up-regulated the expression of PECAM-1 in HUVECs but did not affect gelatinase secretion. Finally, in PBMCs, progelatinase B production was increased by soluble PECAM-1 mAb, recombinant PECAM-1, LPS, and PMA, whereas IFN-beta reduced gelatinase B secretion. IFN-beta did not alter PECAM-1 expression on PBMCs. Thus, PECAM-1 and gelatinase B are differently regulated in leukocytes and endothelial cells.
Nelissen
Inge
I
Rega Institute for Medical Research, Laboratory of Molecular Immunology, University of Leuven, B-3000 Leuven, Belgium.
Ronsse
Isabelle
I
Van Damme
Jo
J
Opdenakker
Ghislain
G
D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000201:enzymology*; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D007155:Immunologic Factors / Q000494:pharmacology*; D016899:Interferon-beta / Q000494:pharmacology*; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis* / Q000235:genetics; D009000:Monocytes / Q000201:enzymology*; D009928:Organ Specificity; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000494:pharmacology; D015854:Up-Regulation
D007155:Immunologic Factors; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D011994:Recombinant Proteins; D016899:Interferon-beta; D020780:Matrix Metalloproteinase 9