Regulation of monocyte chemotactic protein-1 expression in human endometrial stromal cells by integrin-dependent cell adhesion

Shed menstrual endometrium is viable and has the ability to implant and gro w in women, who eventually develop endometriosis. Many of the cell-to-cell or cell to-extracellular matrix (ECM) connections are mediated by integrins . Monocyte chemotactic protein (MCP)-1, a potent chemotactic factor produce d in many cell types, is elevated in the peritoneal fluid of women with end ometriosis. In this study, we investigated whether endometrial stromal cell (ESC) adhesion itself induces the expression of MCP-1 and whether this pro cess is integrin mediated. ESC were plated on Petri dishes and 24-well plat es coated with fibronectin, laminin, collagen IV, poly-L-lysine, or mouse a nti-human integrin beta(1) and beta(2) monoclonal antibodies. Adherence of ESC to various ECM substrates, except for poly-L-lysine, a non-integrin-dep endent adhesion matrix, induced the expression of MCP-I at both mRNA and pr otein levels. Engagement of beta(1)-containing integrins was associated wit h ESC adhesion and resulted in up-regulation of MCP-1 gene expression and p rotein secretion. Disruption of the actin cytoskeleton by treating ESC with cytochalasin D completely blocked the increase of MCP-1 induced in respons e to integrin activation. These findings indicate a novel mechanism of MCP- 1 regulation. Cell adhesion to ECM is an important event that leads to stim ulation of MCP-1 expression, and this process is mediated by integrins.