Interleukin-8 expression in endometrial stromal cells is regulated by integrin-dependent cell adhesion

Concentrations of interleukin (IL)-8, a potent chemotactic factor produced by many cell types, are elevated in the peritoneal fluid of women with endo metriosis. We investigated whether endometrial stromal cell (ESC) adhesion induces the expression of IL-8 and if this process is integrin-mediated. ES Cs were plated onto culture dishes coated with various extracellular matrix (ECM) substrates, such as fibronectin, laminin, collagen IV, and poly-L-ly sine, or mouse anti-human integrin beta(1), and beta(2) monoclonal antibodi es. IL-8 expression was induced by adherence of ESCs to fibronectin or coll agen IV, but not to poly-L-lysine, a non-integrin-dependent adhesion matrix . Engagement of beta(1)-containing integrins was associated with ESC adhesi on and resulted in up-regulation of IL-8 mRNA expression and protein secret ion. Disruption of the actin cytoskeleton by treating ESC with cytochalasin D completely blocked the increase of IL-8 that was induced in response to integrin activation, These findings indicate a novel mechanism of IL-8 regu lation; cell adhesion to ECM is an important event that leads to stimulatio n of IL-8 expression, and this process is mediated by integrins.