MCP-1 exerts the inflammatory response via ILK activation during endometriosis pathogenesis

• Published in: Life sciences (1973) 2024-09, Vol.353, p.122902, Article 122902
• Main Authors: Soni, Upendra Kumar, Tripathi, Rupal, Jha, Rajesh Kumar
• Format: Article
• Language: English
• Subjects: 3D spheroids; Animals; CCL; Cell aggregation; Cell Differentiation; Cell invasion; Cell migration; Cell Movement; Chemokine CCL2 - metabolism; Chronic inflammation; CXCL; Disease Models, Animal; ECM; Endometriosis - immunology; Endometriosis - metabolism; Endometriosis - pathology; Female; Humans; IL-10; IL-12; IL-6; Inflammation - metabolism; Inflammation - pathology; Integrin-linked kinase; Macrophages; Macrophages - immunology; Macrophages - metabolism; MCP-1; Mice; Mice, Inbred C57BL; Monocytes; Pelvic endometriosis; Protein Serine-Threonine Kinases - metabolism; Signal Transduction; Tc cells; Th cells; TNF-α; Treg cells
• ISSN: 0024-3205; 1879-0631; 1879-0631
• DOI: 10.1016/j.lfs.2024.122902

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. 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. 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. 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. [Display omitted] •MCP-1 via ILK increases the endometriotic cells colonization, adhesion and invasion.•MCP-1 promotes inflammatory response in mouse model of endometriosis.•ILK inhibition reverses the MCP-1 mediated inflammatory responses.•The altered T-cells by MCP-1 are restored by ILK inhibition in endometriosis.