{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T21:35:10Z","timestamp":1791581710386,"version":"4.3.4"},"reference-count":36,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,5,6]],"date-time":"2026-05-06T00:00:00Z","timestamp":1778025600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["82571900"],"award-info":[{"award-number":["82571900"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"award":["82571900"],"award-info":[{"award-number":["82571900"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Baoshan District Science and Technology Committee, Shanghai","award":["2024-E-30"],"award-info":[{"award-number":["2024-E-30"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Endometriosis is a chronic inflammatory disorder affecting approximately 10% of reproductive-age women, yet non-hormonal therapeutic options remain limited. This study investigates the role of the TLR4\/NF-\u03baB\/NLRP3 inflammasome axis in endometriosis pathogenesis and evaluates the therapeutic potential of pharmacologic TLR4 inhibition. Ectopic endometriotic tissues, eutopic endometrium, and peritoneal fluid were collected from 15 patients with ovarian endometriosis and 15 control subjects. The endometriotic epithelial cell line 11Z was stimulated with LPS and ATP with or without the TLR4 inhibitor TAK-242. A murine endometriosis model was established in wild-type C57BL\/6 and TLR4\u2212\/\u2212 mice treated with TAK-242. Expression of TLR4, p-p65, NLRP3, caspase-1, cleaved caspase-1 (p20), GSDMD-N, IL-1\u03b2, PCNA, and CD31 was assessed by qPCR, Western blot, IHC, and ELISA. Ectopic lesions showed significantly elevated TLR4\/NF-\u03baB\/NLRP3\/IL-1\u03b2 signaling compared with eutopic and control endometrium (all p &lt; 0.05). Peritoneal fluid IL-1\u03b2 was increased in patients, indicating a localized pelvic inflammatory response. In vitro, TAK-242 suppressed LPS\/ATP-induced NF-\u03baB\/NLRP3 activation, pyroptosis, and IL-1\u03b2 secretion (p &lt; 0.05). Furthermore, the NLRP3-specific inhibitor MCC950 confirmed the essential role of NLRP3 inflammasome activation in IL-1\u03b2 maturation. In vivo, TLR4 deletion or TAK-242 treatment reduced lesion weight, PCNA proliferation, and CD31 microvessel density (all p &lt; 0.05). TLR4 inhibition blocks NF-\u03baB nuclear translocation and subsequent inflammasome activation, suggesting a potential role in attenuating inflammation and angiogenesis. The TLR4\/NF-\u03baB\/NLRP3 axis may drive endometriosis progression by linking innate immunity, inflammasome activation, pyroptosis, with possible involvement in angiogenesis warranting further investigation. Pharmacological inhibition of TLR4 attenuates lesion growth, supporting TLR4 as a promising non-hormonal therapeutic target for endometriosis.<\/jats:p>","DOI":"10.3390\/ijms27094151","type":"journal-article","created":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T09:03:37Z","timestamp":1778144617000},"page":"4151","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Targeting TLR4 Attenuates Endometriosis Progression by Suppressing NF-\u03baB\/NLRP3 Inflammasome Activation and Angiogenesis"],"prefix":"10.3390","volume":"27","author":[{"given":"Yunlei","family":"Cao","sequence":"first","affiliation":[{"name":"Department of General Gynecology, Obstetrics & Gynecology Hospital of Fudan University, Shanghai Key Lab of Reproduction and Development, Shanghai Key Lab of Female Reproductive Endocrine Related Diseases, Shanghai 200433, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangxiang","family":"Zhu","sequence":"additional","affiliation":[{"name":"School of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinxin","family":"Hou","sequence":"additional","affiliation":[{"name":"School of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ding","family":"Ding","sequence":"additional","affiliation":[{"name":"Department of General Gynecology, Obstetrics & Gynecology Hospital of Fudan University, Shanghai Key Lab of Reproduction and Development, Shanghai Key Lab of Female Reproductive Endocrine Related Diseases, Shanghai 200433, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"104213","DOI":"10.1016\/j.jri.2024.104213","article-title":"PI3K\/AKT signaling pathway associates with pyroptosis and inflammation in patients with endometriosis","volume":"162","author":"An","year":"2024","journal-title":"J. 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