目的:MCP-1在子宫内膜异位症中升高。ILK在几种细胞事件中起作用并与MCP-1信号传导相互作用。在目前的研究中,我们评估了MCP-1-ILK信号在人子宫内膜异位细胞中的作用(Hs832(C)。TC)定殖的潜力,入侵,附着力,等。子宫内膜异位症小鼠模型中巨噬细胞的分化以及炎症。
方法:通过注射MCP-1建立MCP-1水平升高的子宫内膜异位症小鼠模型。我们检查了迁移,附着力,Hs832(C)的定殖和入侵。响应于MCP-1-ILK信令的TC。我们还检查了响应于MCP-1-ILK信号传导的THP-1细胞向巨噬细胞的分化。
结果:我们观察到MCP-1增加了Hs832(C)中ILK的Ser246磷酸化。TC并增强了迁移,附着力,殖民,和入侵Hs832(C)。TC。在子宫内膜异位症小鼠模型中,我们发现趋化因子(CCL-11,CCL-22和CXCL13)水平升高。MCP-1介导的ILK激活水平升高,导致增加的炎症反应和住宅和循环巨噬细胞的浸润,和单核细胞分化,但抑制了抗炎反应.ILK的抑制剂(CPD22)通过恢复Hs832(C)而逆转MCP-1介导的作用。TCs和THP-1表型。子宫内膜异位症小鼠模型中的ILK抑制降低了MCP-1介导的促炎细胞因子的作用,但随着T调节和T辅助细胞恢复,抗炎反应增加。
结论:靶向ILK可恢复腹膜腔和子宫内膜组织中的MCP-1环境,减少炎症反应,改善子宫内膜异位症小鼠模型中的T调节和T辅助细胞,并减少迁移,附着力,子宫内膜异位细胞的定植和侵袭。
OBJECTIVE: MCP-1 has been shown to be elevated in endometriosis. ILK functions in several cellular events and interacts with MCP-1-signaling. In the current study, we evaluated the role of MCP-1-ILK signaling in human endometriotic cell\'s (Hs832(C).TCs) potential for colonization, invasion, adhesion, etc. and differentiation of macrophage along with inflammation in an endometriosis mouse model.
METHODS: A mouse model of endometriosis with elevated levels of MCP-1 was developed by injecting MCP-1. We examined the migration, adhesion, colonization and invasion of Hs832(C).TCs in response to MCP-1-ILK signaling. We also examined the differentiation of THP-1 cells to macrophage in response to MCP-1-ILK signaling.
RESULTS: We observed that MCP-1 increased Ser246 phosphorylation of ILK in Hs832(C).TCs and enhanced the migration, adhesion, colonization, and invasion of Hs832(C).TCs. In the mouse model of endometriosis, we found elevated chemokines (CCL-11, CCL-22 and CXCL13) levels. An increased level of MCP-1 mediated ILK activation, leading to increased inflammatory reaction and infiltration of residential and circulatory macrophages, and monocyte differentiation, but suppressed the anti-inflammatory reaction. The inhibitor (CPD22) of ILK reversed the MCP-1-mediated action by restoring Hs832(C).TCs and THP-1 phenotype. ILK inhibition in a mouse model of endometriosis reduced the effects of MCP-1 mediated pro-inflammatory cytokines, but increased anti-inflammatory response along with T-regulatory and T-helper cell restoration.
CONCLUSIONS: Targeting ILK restores MCP-1 milieu in the peritoneal cavity and endometrial tissues, reduces the inflammatory response, improves the T-regulatory and T-helper cells in the endometriosis mouse model and decreases the migration, adhesion, colonization and invasion of endometriotic cells.