Garcia-Velasco J A, Seli E, Arici A
Department of Obstetrics and Gynecology, Yale University School of Medicine, New Haven, Connecticut 06520-8063, USA.
Biol Reprod. 1999 Aug;61(2):548-52. doi: 10.1095/biolreprod61.2.548.
Shed menstrual endometrium is viable and has the ability to implant and grow 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 produced in many cell types, is elevated in the peritoneal fluid of women with endometriosis. In this study, we investigated whether endometrial stromal cell (ESC) adhesion itself induces the expression of MCP-1 and whether this process is integrin mediated. ESC were plated on Petri dishes and 24-well plates coated with fibronectin, laminin, collagen IV, poly-L-lysine, or mouse anti-human integrin beta(1) and beta(2) monoclonal antibodies. Adherence of ESC to various ECM substrates, except for poly-L-lysine, a non-integrin-dependent adhesion matrix, induced the expression of MCP-1 at both mRNA and protein levels. Engagement of beta(1)-containing integrins was associated with ESC adhesion and resulted in up-regulation of MCP-1 gene expression and protein secretion. Disruption of the actin cytoskeleton by treating ESC with cytochalasin D completely blocked the increase of MCP-1 induced in response to integrin activation. These findings indicate a novel mechanism of MCP-1 regulation. Cell adhesion to ECM is an important event that leads to stimulation of MCP-1 expression, and this process is mediated by integrins.
脱落的月经子宫内膜具有活性，能够在女性体内着床并生长，最终导致子宫内膜异位症的发生。许多细胞间或细胞与细胞外基质（ECM）的连接是由整合素介导的。单核细胞趋化蛋白（MCP）-1是一种在多种细胞类型中产生的强效趋化因子，在子宫内膜异位症患者的腹水中含量升高。在本研究中，我们调查了子宫内膜基质细胞（ESC）黏附本身是否会诱导MCP-1的表达，以及该过程是否由整合素介导。将ESC接种在涂有纤连蛋白、层粘连蛋白、IV型胶原、聚-L-赖氨酸或小鼠抗人整合素β(1)和β(2)单克隆抗体的培养皿和24孔板上。ESC与各种ECM底物的黏附，除了聚-L-赖氨酸这种非整合素依赖性黏附基质外，均在mRNA和蛋白质水平上诱导了MCP-1的表达。含β(1)整合素的结合与ESC黏附相关，并导致MCP-1基因表达上调和蛋白质分泌增加。用细胞松弛素D处理ESC破坏肌动蛋白细胞骨架，完全阻断了整合素激活诱导的MCP-1增加。这些发现表明了一种新的MCP-1调节机制。细胞与ECM的黏附是导致MCP-1表达受刺激的重要事件，且该过程由整合素介导。
