Integrin-mediated stimulation of monocyte chemotactic protein-1 expression.
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 beta1-integrin subunit, demonstrating that ligation of beta1-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.
Marra
F
F
Istituto di Medicina Interna, Università di Firenze, Florence, Italy. f.marra@dfc.unifi.it
Pastacaldi
S
S
Romanelli
R G
RG
Pinzani
M
M
Ticali
P
P
Carloni
V
V
Laffi
G
G
Gentilini
P
P
D002448:Cell Adhesion; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000096:biosynthesis*; D002634:Chemotaxis, Leukocyte; D003094:Collagen; D005109:Extracellular Matrix / Q000502:physiology*; D005353:Fibronectins; D005786:Gene Expression Regulation; D006801:Humans; D066298:In Vitro Techniques; D016023:Integrins / Q000502:physiology*; D007963:Leukocytes, Mononuclear / Q000502:physiology*; D008099:Liver / Q000166:cytology* / Q000502:physiology*; D008648:Mesoderm / Q000166:cytology / Q000502:physiology; D015203:Reproducibility of Results
D018932:Chemokine CCL2; D005353:Fibronectins; D016023:Integrins; D003094:Collagen