{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,11]],"date-time":"2026-10-11T03:10:00Z","timestamp":1791688200164,"version":"4.3.4"},"reference-count":34,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2025,8,16]],"date-time":"2025-08-16T00:00:00Z","timestamp":1755302400000},"content-version":"vor","delay-in-days":15,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["NIH NIGMS R01GM102146"],"award-info":[{"award-number":["NIH NIGMS R01GM102146"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,8,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Severe trauma releases damage-associated molecular patterns (DAMPs), which activate the immune system via pattern recognition receptors. This triggers inflammatory cascades that can lead to systemic inflammatory response syndrome, immunosuppression, and multiple organ dysfunction syndrome. Pyroptosis is an inflammatory form of cell death mediated by caspase-11 and gasdermin D (GsdmD). In this study, we examined caspase-11's effects on inflammation, tissue damage, and neutrophil infiltration in a model of severe tissue injury. Male C57BL\/6J (WT), caspase-11\u2212\/\u2212, cell-specific caspase-11\u2212\/\u2212 mice (endothelial-specific caspase-11\u2212\/\u2212 [casp11EC\u2212\/\u2212]), platelet-specific caspase-11\u2212\/\u2212 (casp11plt\u2212\/\u2212), and hepatocyte-specific caspase-11\u2212\/\u2212 (casp11HC\u2212\/\u2212) mice were subjected to polytrauma, consisting of hemorrhagic shock (25% total blood volume removed), liver crush, and bilateral lower extremity injury. At 6\u2005h post-polytrauma, blood, plasma, and tissues were collected for analysis. Western blot analysis showed caspase-11 and GsdmD cleavage in the lungs and liver in WT mice at 6\u2005h after polytrauma. GsdmD cleavage was found to be caspase-11 dependent. Inflammatory mediators, plasma IL-6 and CXCL-1\/KC, were significantly increased in caspase-11\u2212\/\u2212, casp11HC\u2212\/\u2212 and casp11EC\u2212\/\u2212 mice compared to WT controls or casp11plt\u2212\/\u2212. Liver damage (ALT\/AST) was similar between groups. Circulating neutrophil counts were decreased in caspase-11\u2212\/\u2212, but neutrophils and neutrophil myeloperoxidase levels were increased in caspase-11\u2212\/\u2212 liver compared with WT after polytrauma. Our study identifies an unexpected and novel anti-inflammatory function for caspase-11 in trauma, through the regulation of neutrophil influx into tissues. Our findings underscore the significance of caspase-11 activation early after polytrauma to moderate trauma-induced inflammation.<\/jats:p>","DOI":"10.1093\/jleuko\/qiaf121","type":"journal-article","created":{"date-parts":[[2025,8,16]],"date-time":"2025-08-16T11:33:53Z","timestamp":1755344033000},"source":"Crossref","is-referenced-by-count":2,"title":["Caspase-11 regulates systemic inflammation and cell death in a cell-specific manner after trauma with shock"],"prefix":"10.1093","volume":"117","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3872-0404","authenticated-orcid":false,"given":"Joud","family":"Mulla","sequence":"first","affiliation":[{"name":"Department of Surgery, University of Pittsburgh School of Medicine , 200 Lothrop Street, Pittsburgh, PA 15213 ,","place":["United States"]},{"name":"Department of Pathology, University of Pittsburgh School of Medicine , 200 Lothrop Street, Pittsburgh, PA 15261 ,","place":["United 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