title: Adhesion of human monocytic THP-1 cells to endothelial cell adhesion molecules or extracellular matrix proteins via beta1 integrins regulates heparin binding epidermal growth factor-like growth factor (HB-EGF) expression.
abstract: Adherence to endothelium and then to the extracellular matrix is a prerequisite for extravasation of monocytes into injured tissues. There, monocytes differentiate into macrophages and express heparin binding epidermal growth factor-like growth factor (HB-EGF), a key growth factor involved in normal wound healing. We investigated whether the interaction of human monocytic THP-1 cells with the endothelial cell adhesion molecules (vascular CAM-1, VCAM-1; intercellular adhesion molecule-1 ICAM-1 and endothelial-selectin, E-selectin), or the extracellular matrix (ECM) proteins (fibronectin, FN; laminin, LN and fibrinogen, FG) regulate HB-EGF expression. We have shown that adherence of THP-1 cells via VCAM-1, E-selectin or FN, which are all overexpressed at sites of inflammation, potentiates HB-EGF mRNA expression. In contrast, adhesion of THP-1 cells via ICAM-1 or FG, has no significant effect. Since THP-1 cells interact with ICAM-1 and FG through beta2 integrins, and with VCAM-1 and FN via beta1 integrins, regulation of HB-EGF expression appears to be specific to beta1 integrin ligation. In addition, we demonstrate that THP-1 binding to LN, through the beta1 integrin VLA-6, down regulates HB-EGF expression. Thus physiologically, transient destruction of LN and expression of VCAM-1, E-selectin and fibronectin at sites of inflammation, may locally induce HB-EGF overexpression.
authors.affiliation: INSERM U. 364, 06107 Nice Cedex 02, France.
authors.forename: B
authors.initials: B
authors.lastname: Mograbi
authors.forename: N
authors.initials: N
authors.lastname: Rochet
authors.forename: C
authors.initials: C
authors.lastname: Emiliozzi
authors.forename: B
authors.initials: B
authors.lastname: Rossi
mesh_terms: D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000818:Animals; D019556:COS Cells; D002448:Cell Adhesion / Q000502:physiology*; D015815:Cell Adhesion Molecules / Q000502:physiology*; D002460:Cell Line; D005576:Colforsin / Q000494:pharmacology; D019040:E-Selectin / Q000502:physiology; D004730:Endothelium, Vascular / Q000502:physiology*; D004815:Epidermal Growth Factor / Q000235:genetics*; D016326:Extracellular Matrix Proteins / Q000502:physiology*; D005786:Gene Expression Regulation / Q000187:drug effects; D006493:Heparin / Q000378:metabolism; D066257:Heparin-binding EGF-like Growth Factor; D006801:Humans; D019012:Integrin beta1 / Q000502:physiology*; D018799:Intercellular Adhesion Molecule-1 / Q000502:physiology; D036341:Intercellular Signaling Peptides and Proteins; D009000:Monocytes; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014158:Transcription, Genetic / Q000187:drug effects; D014162:Transfection; D019010:Vascular Cell Adhesion Molecule-1 / Q000502:physiology
chemical_list: D015815:Cell Adhesion Molecules; D019040:E-Selectin; D016326:Extracellular Matrix Proteins; C587883:HBEGF protein, human; D066257:Heparin-binding EGF-like Growth Factor; D019012:Integrin beta1; D036341:Intercellular Signaling Peptides and Proteins; D012333:RNA, Messenger; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D005576:Colforsin; D015124:8-Bromo Cyclic Adenosine Monophosphate; D015240:Phorbol 12,13-Dibutyrate; D004815:Epidermal Growth Factor; D006493:Heparin; D013755:Tetradecanoylphorbol Acetate