{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T04:25:34Z","timestamp":1786940734551,"version":"build-2736575974"},"reference-count":44,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,8,16]],"date-time":"2026-08-16T00:00:00Z","timestamp":1786838400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,8,16]],"date-time":"2026-08-16T00:00:00Z","timestamp":1786838400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82072232"],"award-info":[{"award-number":["82072232"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82572459"],"award-info":[{"award-number":["82572459"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003453","name":"Natural Science Foundation of Guangdong Province","doi-asserted-by":"publisher","award":["2024A1515012818"],"award-info":[{"award-number":["2024A1515012818"]}],"id":[{"id":"10.13039\/501100003453","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012226","name":"Fundamental Research Funds for the Central Universities","doi-asserted-by":"publisher","award":["21623114"],"award-info":[{"award-number":["21623114"]}],"id":[{"id":"10.13039\/501100012226","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"abstract":"\n Background and Purpose<\/jats:title>\n Cullin 4B (Cul4B), a scaffold protein of CUL4B\u2010RING E3 ligase complex, functions primarily as a negative regulator of inflammation. This study aims to investigate its role in acute lung injury (ALI) and NLRP3 ubiquitination.<\/jats:p>\n <\/jats:sec>\n \n Experimental approach<\/jats:title>\n Cul4B expression and distribution were examined in two sepsis\u2010induced ALI mouse models. Lung\u2010specific overexpression and myeloid\u2010specific Cul4B deletion were applied to evaluate its effects on lung histopathology, pulmonary inflammation, and alveolar capillary barrier dysfunction. The role of Cul4B in NLRP3 inflammasome activation was evaluated in THP\u20101 cells and Cul4B\u2010deficient BMDMs. Cul4B\u2010NLRP3 interaction and Cul4B\u2010mediated NLRP3 ubiquitination were determined. The involvement of Cul4B in MN\u201008\u2010mediated ALI protection and inflammasome suppression was also investigated.<\/jats:p>\n <\/jats:sec>\n \n Key results<\/jats:title>\n Cul4B was significantly downregulated in lung tissues of sepsis\u2010induced ALI mice. Pulmonary overexpression of Cul4B attenuated lung injury and inflammation, whereas myeloid\u2010specific deletion of Cul4B exacerbated epithelial barrier damage and inflammatory responses, along with enhanced Nigericin\u2010induced NLRP3 inflammasome activation. Cul4B was shown to interact with both endogenous and exogenous NLRP3 and suppressed NLRP3 inflammasome activation by promoting NLRP3 ubiquitination. MN\u201008, a small molecule previously reported to alleviate lipopolysaccharide (LPS)\u2010induced ALI, was found to upregulate Cul4B expression and inhibit NLRP3 inflammasome activation by promoting NLRP3 ubiquitination.<\/jats:p>\n <\/jats:sec>\n \n Conclusions and implications<\/jats:title>\n Upregulating Cul4B promotes NLRP3 ubiquitination, thereby inhibiting inflammasome activation and mitigating pulmonary epithelial barrier dysfunction and inflammation in ALI. Cul4B emerges as a potential therapeutic target, and these findings provide new insights into the mechanism by which MN\u201008 protects against sepsis\u2010induced ALI.<\/jats:p>\n <\/jats:sec>","DOI":"10.1111\/bph.70605","type":"journal-article","created":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T04:06:51Z","timestamp":1786939611000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Cul4B up\u2010regulation attenuates sepsis\u2010induced acute lung injury by promoting NLRP3 ubiquitination and inhibiting NLRP3 inflammasome activation"],"prefix":"10.1111","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2703-4983","authenticated-orcid":false,"given":"Huihui","family":"Hu","sequence":"first","affiliation":[{"name":"State Key Laboratory of Bioactive Molecules and Druggability Assessment; Guangdong Basic Research Center of Excellence for Natural Bioactive Molecules and Discovery of Innovative Drugs College of Pharmacy, Jinan University Guangzhou 510632 China"},{"name":"Department of Intensive Care Unit The First Affiliated Hospital of Jinan University Guangzhou 510630 China"},{"name":"Guangzhou Key Laboratory of Innovative Chemical Drug Research in Cardio\u2010cerebrovascular Diseases; Institute of New Drug Research College of Pharmacy, Jinan University Guangzhou 510632 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiabei","family":"Wang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Bioactive Molecules and Druggability Assessment; Guangdong Basic Research Center of Excellence for Natural Bioactive Molecules and Discovery of Innovative Drugs College of Pharmacy, Jinan University Guangzhou 510632 China"},{"name":"Guangzhou Key Laboratory of Innovative Chemical Drug Research in Cardio\u2010cerebrovascular Diseases; Institute of New Drug Research College of Pharmacy, Jinan University Guangzhou 510632 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuqing","family":"Zhang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Bioactive Molecules and Druggability Assessment; Guangdong Basic Research Center of Excellence for Natural Bioactive Molecules and Discovery of Innovative Drugs College of Pharmacy, Jinan University Guangzhou 510632 China"},{"name":"Guangzhou Key Laboratory of Innovative Chemical Drug Research in Cardio\u2010cerebrovascular Diseases; Institute of New Drug Research College of Pharmacy, Jinan University Guangzhou 510632 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chuanjie","family":"Yao","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Bioactive Molecules and Druggability Assessment; Guangdong Basic Research Center of Excellence for Natural Bioactive Molecules and Discovery of Innovative Drugs College of Pharmacy, Jinan University Guangzhou 510632 China"},{"name":"Guangzhou Key Laboratory of Innovative Chemical Drug Research in Cardio\u2010cerebrovascular Diseases; Institute of New Drug Research College of Pharmacy, Jinan University Guangzhou 510632 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fengzhi","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Intensive Care Unit The First Affiliated Hospital of Jinan University Guangzhou 510630 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangkun","family":"Yuan","sequence":"additional","affiliation":[{"name":"Department of Intensive Care Unit The First Affiliated Hospital of Jinan University Guangzhou 510630 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Intensive Care Unit The First Affiliated Hospital of Jinan University Guangzhou 510630 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zheng","family":"Xiang","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Health Science Center School of Medicine, Jinan University Guangzhou 510632 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guozhen","family":"Cui","sequence":"additional","affiliation":[{"name":"Guizhou Provincial Key Laboratory of Innovation and Manufacturing for Pharmaceuticals School of Bioengineering, Zhuhai Campus of Zunyi Medical University Zhuhai 519041 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mei","family":"Jing","sequence":"additional","affiliation":[{"name":"Guangzhou Magpie Pharmaceuticals Co., Ltd. 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