Genistein enhances the ICAM-mediated adhesion by inducing the expression of ICAM-1 and its counter-receptors.
Binding of circulating cells to endothelium is mediated by recognition between endothelial adhesion molecules and their counter-receptors. The beta 2 integrins are a group of adhesion molecules, mainly expressed on leukocytes, that mediate intercellular binding by recognizing their counterparts on endothelial cells, among others ICAM-1. In this study we have studied the regulation of this interaction in myelomonocytic cells treated with genistein, a tyrosine kinase inhibitor with several other biological functions. We show that genistein upregulates the surface expression of the beta 2-integrins in the monoblastic THP-1 and to a lesser extent in the promyelocytic HL-60 leukemia cell lines. This upregulation leads to an increase in the adherence of THP-1 cells to ICAM-1. Genistein also modulates the expression of ICAM-1 on endothelial cells by potentiating the upregulating effect of TNF and IFN-gamma. Genistein may thus enhance intercellular binding by affecting both the endothelium and the circulating cells.
Tiisala
S
S
Department of Bacteriology and Immunology, University of Helsinki, Finland.
Majuri
M L
ML
Carpén
O
O
Renkonen
R
R
D015703:Antigens, CD / Q000096:biosynthesis; D000970:Antineoplastic Agents / Q000494:pharmacology; D018821:CD18 Antigens; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology*; D015815:Cell Adhesion Molecules / Q000096:biosynthesis*; D002460:Cell Line; D005434:Flow Cytometry; D015870:Gene Expression / Q000187:drug effects*; D019833:Genistein; D006801:Humans; D016023:Integrins / Q000096:biosynthesis*; D018799:Intercellular Adhesion Molecule-1; D007371:Interferon-gamma / Q000494:pharmacology; D007529:Isoflavones / Q000494:pharmacology*; D015473:Leukemia, Promyelocytic, Acute; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D015854:Up-Regulation
D015703:Antigens, CD; D000970:Antineoplastic Agents; D018821:CD18 Antigens; D015815:Cell Adhesion Molecules; D016023:Integrins; D007529:Isoflavones; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D007371:Interferon-gamma; D019833:Genistein