{
  "abstract": "The human body has a remarkable ability to regulate inflammation, a biophysical response triggered by virus infection and tissue damage. Sirt6 is critical for metabolism and lifespan; however, its role in inflammation is unknown. Here we show that Sirt6-null (Sirt6(-/-)) mice developed chronic liver inflammation starting at ∼2 months of age, and all animals were affected by 7-8 months of age. Deletion of Sirt6 in T cells or myeloid-derived cells was sufficient to induce liver inflammation and fibrosis, albeit to a lesser degree than that in the global Sirt6(-/-) mice, suggesting that Sirt6 deficiency in the immune cells is the cause. Consistently, macrophages derived from the bone marrow of Sirt6(-/-) mice showed increased MCP-1, IL-6, and TNFα expression levels and were hypersensitive to LPS stimulation. Mechanistically, SIRT6 interacts with c-JUN and deacetylates histone H3 lysine 9 (H3K9) at the promoter of proinflammatory genes whose expression involves the c-JUN signaling pathway. Sirt6-deficient macrophages displayed hyperacetylation of H3K9 and increased occupancy of c-JUN in the promoter of these genes, leading to their elevated expression. These data suggest that Sirt6 plays an anti-inflammatory role in mice by inhibiting c-JUN-dependent expression of proinflammatory genes.",
  "abstract_shown": true,
  "affiliations": [],
  "article_type": null,
  "arxiv": null,
  "author_total": 13,
  "authors": [
    {
      "name": "Cuiying Xiao"
    },
    {
      "name": "Rui-Hong Wang"
    },
    {
      "name": "Tyler Lahusen"
    },
    {
      "name": "Ogyi Park"
    },
    {
      "name": "Adeline Bertola"
    },
    {
      "name": "Takashi Maruyama"
    },
    {
      "name": "Della Reynolds"
    },
    {
      "name": "Qiang Chen"
    },
    {
      "name": "Xiaoling Xu"
    },
    {
      "name": "Howard Young"
    },
    {
      "name": "Wan-Jun Chen"
    },
    {
      "name": "Bin Gao"
    },
    {
      "name": "Chu-Xia Deng"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/64btvzgcvjeb1.bib",
  "cited_by": 156,
  "doi": "10.1074/jbc.m112.415182",
  "fulltext_url": null,
  "id": "64btvzgcvjeb1",
  "issns": [
    "0021-9258",
    "1083-351X"
  ],
  "landing_url": "https://hal.science/hal-05795804v1",
  "language": "en",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "hal",
      "0.sdv"
    ],
    [
      "openalex",
      "2717|Sirtuins and Resveratrol in Medicine"
    ]
  ],
  "openalex": "W2037034308",
  "pdf_url": "http://www.jbc.org/article/S0021925820438360/pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-12",
  "publisher": "American Society for Biochemistry and Molecular Biology",
  "ris": "https://research.draconitic.com/paper/64btvzgcvjeb1.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:55Z",
      "native_id": "hal-05795804",
      "source": "hal",
      "url": "https://hal.science/hal-05795804v1"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "journal-openalex:1312|Protein Kinase Regulation and GTPase Signaling",
      "subfield": "molecular-biology"
    }
  ],
  "title": "Progression of Chronic Liver Inflammation and Fibrosis Driven by Activation of c-JUN Signaling in Sirt6 Mutant Mice",
  "title_text": "Progression of Chronic Liver Inflammation and Fibrosis Driven by Activation of c-JUN Signaling in Sirt6 Mutant Mice",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:17:55Z",
  "url": "https://research.draconitic.com/paper/64btvzgcvjeb1",
  "venue": "Journal of Biological Chemistry",
  "versions": []
}