Interleukin 6 secretion from activated macrophages promotes the migration of endometriotic epithelial cells


Interleukin 6 secretion from activated macrophages promotes the migration of endometriotic epithelial cells

The communication of macrophages and endometriotic cells may be a key for endometriosis development

Key Points

Highlight:

  • This is the first direct evidence showing that interleukin 6-induces MMP2 and MMP9 expression in endometriotic cells.

Aim:

  • To understand a better mechanism of the actions of the macrophages in endometriosis, the Dr. Choi group investigated the reciprocal activation between endometriotic cells and M2 macrophages

Key points:

  • Endometriotic epithelial cells, not stromal cells, stimulates macrophage migration by secreting soluble factors, CC chemokine ligand 2.
  • M2 macrophages stimulate endometriotic cell migration by interleukin 6.
    • EAMs (endometriosis-associated macrophages) recruited and stimulated by endometriosis may turn into M2 macrophages.
    • M2 macrophages interact with endometriotic cells via a soluble factor, resulting in the progression of endometriosis.
    • Interleukin 6 is linked with the endometriosis-associated macrophages-induced migration of endometriotic cells.
  • Inhibition of interleukin six signaling suppressed MMP2 and MMP9 expression levels in endometriotic cells.
    • MMP2 and MMP9 are type IV collagenases that degrade the principal component of basement membranes.
    • MMP family is known to play an essential role in the migration and invasion of various cells including endometriotic cells.

Limitation:

  • More detailed studies are required to understand the microenvironment of endometriosis.

Lay Summary

Endometriosis is a chronic inflammatory disease. Accumulating evidence suggests that endometriosis patients have a higher level of various inflammatory factors which are associated with the pathogenesis of the disease. Several studies have shown marked increases in macrophage populations and activity in endometriosis patients, suggesting a critical function of macrophage on establishment and progression of endometriosis. Given that endometriosis shares several features with malignant cells, M2 macrophages, tumor-associated macrophages, in endometriosis become more critical.

To have a better understanding of the molecular mechanism underlying the actions of the M2 macrophages in endometriosis, the Dr. Choi group from Kyung Hee University in Korea investigated the reciprocal activation between endometriotic cells and M2 macrophages. 

They found that endometriotic epithelial cells, not stromal cells, stimulates macrophage migration. Among soluble factors secreted by endometriotic epithelial cells, CC chemokine ligand 2 plays an important role to attract macrophages. After the endometriosis-associated macrophages (EAMs) are recruited and stimulated by endometriosis, they turn into M2 macrophages. Theses M2 macrophages interact with endometriotic cells via interleukin 6 and induce MMP2 and MMP9 expression which is highly essential for cell migration and invasion by degrading basement membrane. These enhanced MMP2 and MMP9 promote endometriotic cells to migrate. Once the interleukin six signaling is inhibited, the author found the expression of MMP2 and MMP9 levels in endometriotic cells was suppressed.

Although the interaction between IL6 and MMP2 and MMP9 has been reported in other cells, this is the first direct evidence showing that interleukin 6-induces MMP2 and MMP9 expression in endometriotic cells. Though these findings provide advanced information regarding the microenvironment in endometriosis, more careful studies are required for better understanding, according to Dr. Choi.


Research Source: https://www.ncbi.nlm.nih.gov/pubmed/29036448


Endometriosis Macrophages IL6 CCL2 MMP2/9

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