Related Experiment Video
Updated: Jun 21, 2025
Isolation of Peritoneum-derived Mast Cells and Their Functional Characterization with Ca2+-imaging and Degranulation Assays
Published on: July 4, 2018
MCP-1 exerts the inflammatory response via ILK activation during endometriosis pathogenesis
Upendra Kumar Soni1, Rupal Tripathi2, Rajesh Kumar Jha2
1Endocrinology Division, Council of Scientific and Industrial; Research (CSIR)-Central Drug Research Institute (CDRI), Sector-10, Jankipuram Extension, Sitapur Road, Lucknow 226031, U.P., India.
Insights
Targeting ILK signaling in endometriosis reduces endometriotic cell invasion and inflammation. This approach restores immune balance, improving T-cell function and suppressing pro-inflammatory responses in a mouse model.
Area of Science:
- Reproductive biology
- Immunology
- Cell biology
Background:
- Monocyte chemoattractant protein-1 (MCP-1) is elevated in endometriosis.
- Integrin-linked kinase (ILK) interacts with MCP-1 signaling pathways.
- ILK plays a role in various cellular functions relevant to endometriosis progression.
Purpose of the Study:
- To investigate the role of MCP-1-ILK signaling in endometriotic cell behavior (adhesion, invasion, colonization).
- To evaluate the impact of MCP-1-ILK signaling on macrophage differentiation and inflammation in an endometriosis mouse model.
Main Methods:
- Developed a mouse model of endometriosis by injecting MCP-1.
- Examined endometriotic cell (Hs832(C).TCs) migration, adhesion, colonization, and invasion in response to MCP-1-ILK signaling.
- Assessed THP-1 cell differentiation into macrophages under MCP-1-ILK signaling influence.
Main Results:
- MCP-1 enhanced ILK phosphorylation in endometriotic cells, promoting their migration, adhesion, colonization, and invasion.
- In the endometriosis model, MCP-1-ILK activation increased pro-inflammatory chemokines and macrophage infiltration while suppressing anti-inflammatory responses.
- ILK inhibition (CPD22) reversed these effects, restoring cell phenotypes and promoting anti-inflammatory responses, including T-cell restoration.
Conclusions:
- Targeting ILK normalizes the peritoneal MCP-1 environment in endometriosis.
- ILK inhibition reduces endometriotic cell invasiveness and the inflammatory response.
- This strategy improves T-regulatory and T-helper cell function in endometriosis models.
Aims:
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.
Materials And 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.
Key Findings:
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.
Significance:
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.
More Related Videos
07:20Intraoperative Detection of Subtle Endometriosis: A Novel Paradigm for Detection and Treatment of Pelvic Pain Associated with the Loss of Peritoneal Integrity
Published on: December 21, 2012
08:13Establishment of an Experimental Mouse Model of Endometrioma to Study its Related Infertility
Published on: April 5, 2024
Related Concept Videos
01:31Regulation of the Unfolded Protein Response
01:30Inflammatory Bowel Disease II: Crohn's Disease
Inflammatory bowel disease, commonly known as IBD, refers to a collection of disorders that lead to persistent inflammation of the gastrointestinal tract. The two types of IBD are ulcerative colitis, which impacts the colon, and Crohn's disease, which can involve any part of the gastrointestinal segment.
Crohn's disease
Crohn's disease is a chronic, systemic inflammatory bowel disease (IBD) that predominantly affects the gastrointestinal tract. It is marked by...
01:27Inflammatory Bowel Disease I: Ulcerative Colitis
Inflammatory bowel disease, or IBD, encompasses a group of disorders characterized by chronic inflammation or ulceration of the gastrointestinal tract.
Risk Factors
The exact cause of IBD remains unclear, although it is believed to be due to a mix of genetic, environmental, microbial, and immune factors. Genetic factors are significant in determining susceptibility to IBD, with family history being a critical risk factor. Individuals with a first-degree relative who has IBD are at...