Endometriosis is an inflammation-dependent disease which shares similarities with malignant tumors including attachment and infiltration. Tripartite motif containing 24 (TRIM24) has been illustrated in inflammatory responses and gynecological tumors, and Nod-like receptor protein 3 (NLRP3) inflammasome has been implicated in endometriosis. However, the involvement of TRIM24 and the role of NLRP3/Caspase-1/interleukin-1β (IL-1β)-mediated pyroptosis in endometriosis remain obscure. In this study, we originally detected the decreased expression of TRIM24 in ectopic endometrium of endometriosis (EMS) compared with normal endometrium (NE). Then we measured the promoted protein expression of pyroptotic biomarkers (NLRP3, Pro-Caspase-1, Caspase-1, Pro-IL-1β and IL-1β) using Western blot, and the stimulated secretion of IL-1β and IL-18 by enzyme-linked immunosorbent assay (ELISA) in ectopic human endometrial stromal cells (hESC) compared with normal hESC. TRIM24-small-interfering RNA (siTRIM24) was used to silence TRIM24, while TRIM24-pcDNA3.1 was for overexpressing TRIM24. The migration of hESC was determined by Transwell migration assay. Co-immunoprecipitation and ubiquitination analysis were conducted to explore the interaction between TRIM24 and NLRP3. Subsequently, we found that TRIM24 negatively regulated NLRP3/Caspase-1/IL-1β-mediated pyroptosis and cell migration of hESC, and CY-09, the specific inhibitor of NLRP3, could reverse the promoted pyroptosis and cell migration induced by siTRIM24. Furthermore, TRIM24 interacted with NLRP3 and the upregulation of TRIM24 facilitated the ubiquitination of NLRP3 in ectopic hESC. Our findings suggest that TRIM24 may participate in the progression of endometriosis through NLRP3/Caspase-1/IL-1β-mediated pyroptotic pathway via ubiquitination of NLRP3, which reveals the significant molecular mechanism underlying endometriosis. This article is protected by copyright. All rights reserved.
This article is protected by copyright. All rights reserved.