{
  "abstract": "Noncanonical inflammasome activation mediated by caspase-11 drives macrophage pyroptosis and inflammatory amplification in sepsis, but endogenous restraining mechanisms remain incompletely understood. Here, we investigated the role of Nur77 (NR4A1) in cytosolic LPS-induced pyroptotic signaling using RAW264.7 macrophages and an early cecal ligation and puncture (CLP) sepsis model. LPS priming followed by cytosolic LPS stimulation increased Nur77 expression, caspase-11 cleavage, GSDMD processing, lactate dehydrogenase release, and IL-1β release. Nur77 knockdown aggravated membrane damage, increased GSDMD-N generation and pyroptosis-associated cells, and enhanced IL-1β and IL-18 release. Conversely, Nur77 overexpression attenuated caspase-11/GSDMD-associated readouts and reduced pyroptosis-associated injury. This stimulation condition also increased pannexin-1 and P2 × 7 expression, extracellular ATP release, and Yo-PRO-1 uptake; and these changes were amplified by Nur77 deficiency and blunted by Nur77 overexpression. Wedelolactone treatment attenuated caspase-11-associated readouts and was accompanied by reduced pannexin-1/P2 × 7-related responses. In vivo, pharmacological modulation of Nur77 in the early CLP model was associated with corresponding changes in systemic IL-1β/IL-18 levels, lung, liver, and kidney injury, and caspase-11/GSDMD-associated readouts. Collectively, these findings support a model in which Nur77 acts as an endogenous negative modulator of caspase-11/GSDMD-associated pyroptotic signaling and inflammatory amplification during early sepsis.\n\nSupplementary Information: The online version contains supplementary material available at https://doi.org/10.1007/s10753-026-02568-6.",
  "abstract_shown": true,
  "affiliations": [
    "¹Department of Intensive Care Medicine, the Affiliated Hospital of Guizhou Medical University, Guiyang, 550004 China",
    "²Center for Tissue Engineering and Stem Cell Research, Guizhou Medical University, Ankang Avenue, Guian New District, Guizhou, 561113 China",
    "³Key Laboratory for Research on Autoimmune Diseases of Higher Education Schools in Guizhou Province, 6 Ankang Avenue, Guian New District, Guizhou, 561113 China"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 7,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Changzhen Yang"
    },
    {
      "affs": [
        0
      ],
      "name": "Jiakai Wang"
    },
    {
      "affs": [
        0
      ],
      "name": "Hongying Bi"
    },
    {
      "affs": [
        0
      ],
      "name": "Jianyu Fu"
    },
    {
      "affs": [
        0
      ],
      "name": "Xian Liu"
    },
    {
      "affs": [
        1,
        2
      ],
      "name": "Min Su"
    },
    {
      "affs": [
        0
      ],
      "name": "Xu Liu"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/ea7v804ryj76s.bib",
  "cited_by": 0,
  "doi": "10.1007/s10753-026-02568-6",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13736441/",
  "id": "ea7v804ryj76s",
  "issns": [
    "0360-3997",
    "1573-2576"
  ],
  "landing_url": "https://doi.org/10.1007/s10753-026-02568-6",
  "language": "en",
  "licence": "CC-BY-NC-ND-4.0",
  "licence_label": "CC BY-NC-ND 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Research"
    ],
    [
      "openalex",
      "1312|Inflammasome and immune disorders"
    ]
  ],
  "openalex": "W7201856321",
  "pdf_url": null,
  "pmcid": "PMC13736441",
  "pmid": "42980913",
  "published": "2026-08-08",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/ea7v804ryj76s.ris",
  "sources": [
    {
      "first_seen": "2026-11-09T12:21:53Z",
      "native_id": "PMC13736441",
      "source": "pmc",
      "url": "https://doi.org/10.1007/s10753-026-02568-6"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|Inflammasome and immune disorders",
      "subfield": "molecular-biology"
    }
  ],
  "title": "Nur77 Restrains Caspase-11-associated Macrophage Pyroptosis and Inflammatory Amplification During Early Sepsis",
  "title_text": "Nur77 Restrains Caspase-11-associated Macrophage Pyroptosis and Inflammatory Amplification During Early Sepsis",
  "type": "peer-reviewed",
  "updated_at": "2026-11-09T12:21:53Z",
  "url": "https://research.draconitic.com/paper/ea7v804ryj76s",
  "venue": "Inflammation",
  "versions": []
}