2. Academic Validation
  3. Blockage of the NLRP3 inflammasome by MCC950 inhibits migration and invasion in adenomyosis

Blockage of the NLRP3 inflammasome by MCC950 inhibits migration and invasion in adenomyosis

  • Reprod Biomed Online. 2024 Oct;49(4):104319. doi: 10.1016/j.rbmo.2024.104319.
Yanping Liu 1,  Zhou Jiang 2,  Lu Zhang 3,  Wei Tian 4,  Aimin Lin 5,  Mingjiang Li 6
Affiliations

Affiliations

  • 1 Department of Gynaecology and Obstetrics, Jinan Central Hospital, Shandong University, Jinan, Shandong, People's Republic of China.
  • 2 Department of Reproductive Medicine, Qingdao Women and Children's Hospital, Qingdao, Shandong, People's Republic of China.
  • 3 Department of Gynaecology and Obstetrics, Affiliated Hospital of Jining Medical Univeristy, Jining, Shandong, People's Republic of China.
  • 4 Department of Gynaecology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, People's Republic of China.
  • 5 Department of Gynecology and Obstetrics, Yantai Yuhuangding Hospital, Shandong University, Yantai, Shandong, P.R. China.
  • 6 Department of Gynecology and Obstetrics, Shandong Provincial Hospital, Shandong University, Jinan, Shandong, P. R. China. Electronic address: [email protected].
PMID: 39121559 DOI: 10.1016/j.rbmo.2024.104319
Abstract

Research question: Does the NOD-like Receptor protein 3 (NLRP3) inflammasome have an effect in adenomyosis?

Design: Fresh-frozen endometrial tissues and paraffin specimens were obtained from endometrial tissues from patients with adenomyosis and controls. Western blot, quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemistry (IHC) were applied to assess expression of the NLRP3 inflammasome components. Primary eutopic endometrial stromal cells were isolated from the uteri of patients with adenomyosis. After NLRP3 was knocked down using small interfering RNA, proliferation, invasion and epithelial-mesenchymal transition (EMT) were evaluated using EdU, CCK8, transwell assays and western blot. Importantly, a mouse model of adenomyosis was established to evaluate the effects of the NLRP3 Inhibitor MCC950 on the formation of adenomyosis.

Results: Expression of the NLRP3 inflammasome components was elevated in the ectopic or eutopic endometrium of patients with adenomyosis. NLRP3 knockdown inhibited migration, invasion and EMT in endometrial cells and primary endometrial cells (P < 0.0001). MCC950, which blocks the NLRP3 inflammasome, reduced migration and invasion of endometrial cells (P < 0.01) and primary endometrial cells (P < 0.0001) considerably. Importantly, in the mouse model of adenomyosis, MCC950 had a mitigating effect on the severity of adenomyosis (P < 0.01).

Conclusions: NLRP3 was found to enhance migration, invasion and EMT of human endometrial cells in adenomyosis. Notably, the NLRP3 Inhibitor MCC950 reduced migration and invasion of endometrial cells effectively. Furthermore, in the mouse model of adenomyosis, MCC950 exhibited a therapeutic effect by alleviating the severity of adenomyosis.

Keywords

Adenomyosis; EMT; Invasion; MCC950; Migration; NLRP3.

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