Regulation of Inflammation in Endometriosis

The role of the inflammation in the pathogenesis of endometriosis and the impact of sex hormones in the inflammatory responses

Key Points

Highlight:

• The current understanding of the role of inflammation and the inflammasome in the endometriosis pathogenesis by Dr. García-Gómez group.

Background:

• Endometriosis is an estrogen-dependent and multifaceted gynecological condition that frequently causes chronic and cyclic pelvic pain, and frequently considered an inflammatory disease.
• In most cases, the pain is due to an invasion of endometrial cells and pro-inflammatory mediators on the nerve fibers.
• There is not an actual cure for this disease, and the development of new therapy based on the understanding of endometriosis is highly important.

Key points:

• Hormonal imbalance in endometriosis mainly causes the alterations of multiple cellular functions such as angiogenesis, metabolism, and inflammation.
• The activity of nuclear receptors is also modified in endometriosis.
• The different transcriptomic alterations in endometriosis found the altered gene expression affects inflammatory pathways.
• Inflammasomes are complex molecular structures that control pyroptosis (an inflammatory form of cell death) and the activation of caspase 1, a key enzyme in inflammation.
• Inflammasome component, NLRP3, has been found to interact with the estrogen receptor which activates critical pathways in endometriosis.
• There may be several potential drugs and alternative treatments to inhibit inflammation:
• Crocin is a vegetal compound found in some flowers and saffron, and it possesses anti-inflammatory and anti-proliferation properties.
• Nobiletin, a flavonoid isolated from citrus peels with capacity for inhibiting NF-kB activation.
• Simvastatin, which belongs to the statins family, was also assessed its effect in a baboon model of endometriosis.
• It is still necessary to perform more studies to determine the effectiveness of therapeutical agents in women with endometriosis.
• Further in vivo and clinical studies are necessary for elucidating the pathogenesis of endometriosis.

Lay Summary

Endometriosis is an estrogen-dependent and multifaceted gynecological condition. Unfortunately, this disease frequently causes chronic and cyclic pelvic pain. Though there are several treatments are available, there is not an actual cure for this disease. Therefore, the development of new therapy based on the understanding of endometriosis is highly important. 

Endometriosis is frequently considered as an inflammatory disease. In most cases, the pain is due to an invasion of endometrial cells and pro-inflammatory mediators on the nerve fibers. Therefore, Dr. García-Gómez group from Mexico summarized the current understanding of the role of inflammation and the inflammasome in the endometriosis pathogenesis. This paper was recently published in the journal of “Frontiers in Endocrinology”.

Hormonal imbalance in endometriosis mainly causes the alterations of multiple cellular functions such as angiogenesis, metabolism, and inflammation. Besides enzymatic and hormonal changes, the activity of nuclear receptors is also modified in endometriosis. Furthermore, the different transcriptomic alterations in endometriosis found the altered gene expression affects inflammatory pathways.

Inflammasomes are complex molecular structures that control pyroptosis (an inflammatory form of cell death) and the activation of caspase 1, a key enzyme for inflammation. The alteration of the inflammasome is involved in the development of inflammatory disorders. It has been demonstrated that the human endometrium expresses inflammasome components, including NLRP3 and ASC proteins. NLRP3 has been found to interact with the estrogen receptor. This interaction activates pathways that are critical in endometriosis such as endometriotic cell survival, adhesion, and proliferation and the epithelial-mesenchymal transition pathway.

Based on the understanding, there are several potential drugs and alternative treatments that inhibit inflammation. Crocin is a vegetal compound found in some flowers and saffron, and it possesses anti-inflammatory and anti-proliferation properties. Nobiletin, a flavonoid isolated from citrus peels with capacity for inhibiting NF-kB activation. Simvastatin, which belongs to the statins family, was also assayed its effect in a baboon model of endometriosis

However, it is still necessary to perform more studies to determine the effectiveness of therapeutical agents in women with endometriosis. Especially, further in vivo and clinical studies are necessary for elucidating the pathogenesis of endometriosis.

Research Source: https://pubmed.ncbi.nlm.nih.gov/32063886