{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T20:38:42Z","timestamp":1791664722694,"version":"4.3.4"},"reference-count":51,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2025,8,5]],"date-time":"2025-08-05T00:00:00Z","timestamp":1754352000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Chang Gung Medical Foundation of Taiwan","award":["CMRPG6L0141"],"award-info":[{"award-number":["CMRPG6L0141"]}]},{"name":"Chang Gung Medical Foundation of Taiwan","award":["CMRPG6N0231"],"award-info":[{"award-number":["CMRPG6N0231"]}]},{"name":"Chang Gung Medical Foundation of Taiwan","award":["CMRPG6H0151"],"award-info":[{"award-number":["CMRPG6H0151"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Fat embolism is a critical medical emergency often resulting from long bone fractures or amputations, leading to acute respiratory distress syndrome (ARDS). The NOD-like receptor pyrin domain-containing 3 (NLRP3) inflammasome, a key regulator of innate immunity, is activated by reactive oxygen species and tissue damage, contributing to inflammatory responses. This study examines the role of NLRP3 in fat embolism-induced ARDS and evaluates the therapeutic potential of MCC950, a selective NLRP3 antagonist. Fat embolism was induced by fatty micelle injection into the tail vein of Sprague Dawley rats. Pulmonary injury was assessed through lung weight gain as an edema indicator, NLRP3 expression via Western blot, and IL-1\u03b2 levels using ELISA. Histological damage and macrophage infiltration were evaluated with hematoxylin and eosin staining. Fat embolism significantly increased pulmonary NLRP3 expression, lipid peroxidation, IL-1\u03b2 release, and macrophage infiltration within four hours, accompanied by severe pulmonary edema. NLRP3 was localized in type I alveolar cells, co-localizing with aquaporin 5. Administration of MCC950 significantly reduced inflammatory responses, lipid peroxidation, pulmonary edema, and histological damage, while attenuating MAPK cascade phosphorylation of ERK and Raf. These findings suggest that NLRP3 plays a critical role in fat embolism-induced acute respiratory distress syndrome, and its inhibition by MCC950 may offer a promising therapeutic approach.<\/jats:p>","DOI":"10.3390\/ijms26157571","type":"journal-article","created":{"date-parts":[[2025,8,6]],"date-time":"2025-08-06T07:45:11Z","timestamp":1754466311000},"page":"7571","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["MCC950 Alleviates Fat Embolism-Induced Acute Respiratory Distress Syndrome Through Dual Modulation of NLRP3 Inflammasome and ERK Pathways"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5940-3715","authenticated-orcid":false,"given":"Chin-Kuo","family":"Lin","sequence":"first","affiliation":[{"name":"Division of Pulmonary Infection and Critical Care, Department of Pulmonary and Critical Care Medicine, Chang Gung Memorial Hospital, Chiayi 20401, Taiwan"},{"name":"Graduate Institute of Clinical Medicine Sciences, College of Medicine, Chang Gung University, Taoyuan 33302, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zheng-Wei","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Biochemical Science and Technology, National Chia-Yi University, Chia-Yi 60004, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-Hao","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Biochemical Science and Technology, National Chia-Yi University, Chia-Yi 60004, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1846-1027","authenticated-orcid":false,"given":"Cheng-Ta","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Pulmonary and Critical Care Medicine, Chang Gung Memorial Hospital, Taoyuan 33305, Taiwan"},{"name":"Department of Respiratory Care, College of Medicine, Chang Gung University, Taoyuan 33302, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5548-7675","authenticated-orcid":false,"given":"Chung-Sheng","family":"Shi","sequence":"additional","affiliation":[{"name":"Graduate Institute of Clinical Medicine Sciences, College of Medicine, Chang Gung University, Taoyuan 33302, Taiwan"},{"name":"Division of Colon and Rectal Surgery, Department of Surgery, Chang Gung Memorial Hospital, Chiayi 61363, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chieh-Mo","family":"Lin","sequence":"additional","affiliation":[{"name":"Division of Pulmonary Infection and Critical Care, Department of Pulmonary and Critical Care Medicine, Chang Gung Memorial Hospital, Chiayi 20401, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tzu Hsiung","family":"Huang","sequence":"additional","affiliation":[{"name":"Graduate Institute of Clinical Medicine Sciences, College of Medicine, Chang Gung University, Taoyuan 33302, Taiwan"},{"name":"Department of Respiratory Therapy, Chang Gung Memorial Hospital, Chiayi 61363, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justin Ching Hsien","family":"Lu","sequence":"additional","affiliation":[{"name":"School of Medicine, Fu Jen Catholic University, New Taipei 242062, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kwok-Tung","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Life Science, National Taiwan Normal University, Taipei 10659, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi-Ling","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Biochemical Science and Technology, National Chia-Yi University, Chia-Yi 60004, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1016\/j.bjae.2021.04.003","article-title":"Fat embolism syndrome","volume":"21","author":"Luff","year":"2021","journal-title":"BJA Educ."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"472","DOI":"10.1097\/MAJ.0b013e318172f5d2","article-title":"Fat embolism syndrome","volume":"336","author":"Stein","year":"2008","journal-title":"Am. 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