Integrin-mediated stimulation of monocyte chemotactic protein-1 expression

• Published in: FEBS letters Vol. 414; no. 2; pp. 221 - 225
• Main Authors: Marra, Fabio, Pastacaldi, Sabrina, Romanelli, Roberto G., Pinzani, Massimo, Ticali, Piero, Carloni, Vinicio, Laffi, Giacomo, Gentilini, Paolo
• Format: Journal Article
• Language: English
• Published: England Elsevier B.V 08.09.1997
• Subjects: Cell Adhesion; Cells, Cultured; Chemokine; Chemokine CCL2 - biosynthesis; Chemotaxis, Leukocyte; Collagen; Extracellular Matrix - physiology; Fibronectins; Gene Expression Regulation; Hepatic stellate cell; Humans; In Vitro Techniques; Integrin; Integrins - physiology; Leukocytes, Mononuclear - physiology; Liver - cytology; Liver - physiology; Mesoderm - cytology; Mesoderm - physiology; Monocyte chemotactic protein-1; Reproducibility of Results; Chemokine; Integrin; Hepatic stellate cell; Collagen; Monocyte chemotactic protein-1
• ISSN: 0014-5793; 1873-3468
• DOI: 10.1016/S0014-5793(97)01004-1

We investigated whether activation of integrin receptors could modulate the expression of monocyte chemotactic protein-1 (MCP-1) in human hepatic stellate cells (HSC), mesenchymal cells responsible for extracellular matrix synthesis within the liver. When compared to non-adherent cells, HSC plated on collagen types I or IV, or fibronectin, showed increased MCP-1 gene expression and protein secretion in the conditioned medium. Increased MCP-1 secretion was also observed when cells were plated on dishes coated with a monoclonal antibody directed against the β1-integrin subunit, demonstrating that ligation of β1-integrins is sufficient to stimulate MCP-1 expression. Conversely, integrin-independent cell adhesion on poly- l-lysine did not modify MCP-1 secretion. Disruption of the actin cytoskeleton by cytochalasin D blocked the collagen-dependent increase in MCP-1 secretion. Chemotactic assay of HSC-conditioned medium showed that HSC plated on collagen secrete higher amounts of chemotactic factors for lymphomonocytes, and that MCP-1 accounts for the great majority of this effect. These findings indicate a novel mechanism of MCP-1 regulation possibly relevant in those conditions where HSC interact with an altered extracellular matrix.