{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T21:07:09Z","timestamp":1792789629312,"version":"4.5.0"},"reference-count":68,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2026,2,28]],"date-time":"2026-02-28T00:00:00Z","timestamp":1772236800000},"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":"publisher","award":["82304832"],"award-info":[{"award-number":["82304832"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Yunnan Xingdian Talent Plan Innovation Team Project","award":["202505AS350014"],"award-info":[{"award-number":["202505AS350014"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The liver is a central immunometabolic organ during endotoxemia and a major target of sepsis-related injury. Intriguingly, the liver exhibits a notable resilience to endotoxemia or septic insults, suggesting the activation of endogenous protective mechanisms. The bile acid taurodeoxycholic acid (TDCA) demonstrates hepatoprotective properties; nonetheless, its role and mechanism in lipopolysaccharide (LPS)-driven inflammatory liver injury remain elusive. This study reveals that LPS challenge induces significant reprogramming of hepatic bile acid metabolism, with TDCA being markedly elevated in LPS-challenged mice. In vitro, TDCA dose-dependently attenuated pyroptosis in bone marrow-derived macrophages, as evidenced by reduced lactate dehydrogenase (LDH) release, decreased interleukin-1 beta (IL-1\u03b2) and interleukin-18 (IL-18) secretion, and suppressed dye Oxazole yellow uptake. Consistent with reduced non-canonical inflammasome signaling, TDCA treatment was associated with decreased activation of caspase-11 and its downstream targets Gasdermin D (GSDMD) and IL-1\u03b2. In a lethal D-Galactosamine (D-GalN)\/LPS-induced toxin-sensitized inflammatory liver injury model, therapeutic administration of TDCA (3, 6 mg\/kg) profoundly improved survival rates (40% and 80%, respectively), attenuated liver injury, reduced alanine aminotransferase (ALT) and aspartate aminotransferase (AST), suppressed systemic inflammation (IL-1\u03b2 and IL-18), and ameliorated histopathological damage. Crucially, TDCA treatment reduced the activation of the caspase-11\/GSDMD pathway in the septic liver. Our findings demonstrate that TDCA is an endogenously mobilized bile acid that confers protection against LPS-driven inflammatory liver injury, with effects supporting a role for modulation of the Caspase-11\/GSDMD pyroptotic pathway. These observations provide hypothesis-generating implications for sepsis-associated liver injury that warrant further validation in clinically relevant sepsis models and pathway-necessity studies.<\/jats:p>","DOI":"10.3390\/ijms27052273","type":"journal-article","created":{"date-parts":[[2026,3,2]],"date-time":"2026-03-02T10:24:34Z","timestamp":1772447074000},"page":"2273","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["The Endogenous Metabolite TDCA Ameliorates LPS-Driven Liver Injury via Modulation of Caspase-11\/GSDMD-Mediated Pyroptosis"],"prefix":"10.3390","volume":"27","author":[{"given":"Deqing","family":"Ruan","sequence":"first","affiliation":[{"name":"Yunnan Key Laboratory of Southern Medicine Utilization, Yunnan University of Chinese Medicine, 1076 Yuhua Road, Kunming 650500, China"},{"name":"School of Chinese Materia Medica, Yunnan University of Chinese Medicine, 1076 Yuhua Road, Kunming 650500, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xing","family":"Yan","sequence":"additional","affiliation":[{"name":"Jiangxi Province Key Laboratory of Sustainable Utilization of Traditional Chinese Medicine Resources, Institute of Traditional Chinese Medicine Health Industry, China Academy of Chinese Medical Sciences, Nanchang 330115, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanmei","family":"Tang","sequence":"additional","affiliation":[{"name":"Yunnan Key Laboratory of Southern Medicine Utilization, Yunnan University of Chinese Medicine, 1076 Yuhua Road, Kunming 650500, China"},{"name":"School of Chinese Materia Medica, Yunnan University of Chinese Medicine, 1076 Yuhua Road, Kunming 650500, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shunhua","family":"Yang","sequence":"additional","affiliation":[{"name":"Yunnan Key Laboratory of Southern Medicine Utilization, Yunnan University of Chinese Medicine, 1076 Yuhua Road, Kunming 650500, China"},{"name":"School of Chinese Materia Medica, Yunnan University of Chinese Medicine, 1076 Yuhua Road, Kunming 650500, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinxin","family":"Yang","sequence":"additional","affiliation":[{"name":"Yunnan Key Laboratory of Southern Medicine Utilization, Yunnan University of Chinese Medicine, 1076 Yuhua Road, Kunming 650500, China"},{"name":"School of Chinese Materia Medica, Yunnan University of Chinese Medicine, 1076 Yuhua Road, Kunming 650500, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mei","family":"Zhang","sequence":"additional","affiliation":[{"name":"Yunnan Key Laboratory of Southern Medicine Utilization, Yunnan University of Chinese Medicine, 1076 Yuhua Road, Kunming 650500, China"},{"name":"School of Chinese Materia Medica, Yunnan University of Chinese Medicine, 1076 Yuhua Road, Kunming 650500, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shibo","family":"Yu","sequence":"additional","affiliation":[{"name":"School of Chinese Materia Medica, Yunnan University of Chinese Medicine, 1076 Yuhua Road, Kunming 650500, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Yu","sequence":"additional","affiliation":[{"name":"Yunnan Key Laboratory of Southern Medicine Utilization, Yunnan University of Chinese Medicine, 1076 Yuhua Road, Kunming 650500, China"},{"name":"School of Chinese Materia Medica, Yunnan University of Chinese Medicine, 1076 Yuhua Road, Kunming 650500, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"740","DOI":"10.1177\/0885066617711882","article-title":"Epidemiology and Changes in Mortality of Sepsis After the Implementation of Surviving Sepsis Campaign Guidelines","volume":"34","author":"Andaluz","year":"2019","journal-title":"J. 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