The Role of IL-35 in the Pathogenesis of Endometriosis

This study shows that IL-35 plays a fundamental role in the molecular mechanism that drives endometriosis progression.

Key Points

Highlights:

• This study looks at the role of IL-35 in the disease progression of endometriosis. Additionally, the study hoped to understand the link between endometrial stromal cells (ESCs) and IL-35.
• The researchers also looked at the expression of IL-35 receptors, subunits, and relative messenger RNA to understand how they relate to the pathogenesis of endometriosis.

Importance:

• The molecular mechanism that drives the development endometriosis is still at large.
• Studies such as the one delineated in this article are paramount to better understanding the disease.
• Additionally, comprehension of the mechanism behind disease will make it easier to treat the illness itself.

What’s done here?

• The researchers recruited 37 women with endometriosis and 24 without. They collected peripheral blood (PB), peritoneal fluid (PF), and endometrium from these women, and endometriosis tissues by laparoscopy. 
• IL-35 expression in PB and PF was examined by an enzyme-linked immunosorbent assay.
• Immunohistochemistry (IHC) and quantitative polymerase chain reaction (qPCR) was used to determine the amount of relative messenger RNA and the subunits of IL-35, EBi3, and p35, in the endometrium.

Key results:

• IL-35 expression was up regulated in women with endometriosis and the level of upregulation was dependent on disease progression. Individuals in the later stages of endometriosis had increased expression of IL-35 in the PF.
• Relative messenger RNA and the subunits of IL-35 were found in greater quantities in the endometrium of women with endometriosis.
• ESCs in women with endometriosis, overgrowth of which is the characteristic of the disease, had a greater number of IL-35 receptor subunits, namely IL12Rß2 and gp130. Upregulation of these subunits conversely related to increased proliferation of endometrial stromal cells. 
• Pelvic implants (PI) appear to increase IL-35 expression in individuals with endometriosis.
• The authors of this study believe that IL-35’s role in the development of endometriosis makes it a biomarker for the disease.

Limitations of the study:

• This study was conducted using specimens removed from the participants. In other words, the samples were subject to analysis in an environment unlike their own.
• Other reasons which may alter these biological molecules are not well known and not examined.

Lay Summary

The molecular mechanism that drives endometriosis remains elusive to this day. Zhang et al believe that interleukin 35 (IL-35) plays a role in the pathogenesis of the disease. Their recent publication in Reproductive Sciences titled “Upregulation of Interleukin 35 in Patients With Endometriosis Stimulates Cell Proliferation” delineates the study where they observed the role of IL-35 and IL-35 receptor expression in individuals with endometriosis. 

As a part of the survey, the researchers collected peripheral blood (PB), peritoneal fluid (PF), and endometrium from 37 women with endometriosis and 24 women without endometriosis. IL-35 expression in PB and PF was collected using an enzyme-linked immunosorbent assay. Immunohistochemistry and quantitative polymerase chain reaction was used to determine the amount of relative messenger RNA and the subunits of IL-35, EBi3, and p35, in the endometrium.

The results showed that IL-35 expression was up regulated in women with endometriosis. Additionally, the level of upregulation was dependent on disease progression. The later stages of endometriosis had higher expression of IL-35 in the PF than earlier stages. Furthermore, the relative messenger RNA and the subunits of IL-35 were found in greater quantities in the endometrium of women with endometriosis. The endometrial stromal cells in women with endometriosis tended to have a higher number of IL-35 receptor subunits, namely IL12Rß2 and gp130. Upregulation of these subunits was correlated with an increased proliferation of endometrial stromal cells. Pelvic implants also tended to show increased IL-35 expression in women with endometriosis.

The authors of this study believe that their research identifies IL-35 as a useful biomarker for the proper diagnosis of endometriosis. Unquestionably, this study shows that IL-35 is heavily involved in the progression of endometriosis.

Research Source: https://www.ncbi.nlm.nih.gov/pubmed/28659009