{
  "abstract": "Steatotic liver disease is a common metabolic disorder, and interleukin-1β (IL-1β) contributes to hepatic inflammation and lipid accumulation. ATP-binding cassette subfamily A member 1 (ABCA1) regulates cholesterol efflux and lipid homeostasis. This study examined whether IL-1β suppresses hepatic ABCA1 expression and explored the underlying signaling and transcriptional mechanisms. Primary mouse hepatocytes and HepG2 cells were treated with IL-1β. ABCA1 expression was assessed by Western blotting and RT-qPCR, and ABCA1 promoter activity was examined using luciferase reporter assays with inhibitors targeting phosphoinositide 3-kinase (PI3K), p38 mitogen-activated protein kinase (p38 MAPK), or an H-89-sensitive pathway. Prolactin regulatory element-binding protein (PREB) involvement was evaluated by nuclear protein analysis, PREB-binding-site mutation, and siRNA-mediated knockdown. Lipid accumulation was assessed by intracellular cholesterol measurement and Oil Red O staining. IL-1β decreased ABCA1 protein and mRNA expression in a dose- and time-dependent manner and suppressed ABCA1 promoter activity. Inhibition of p38 MAPK or treatment with H-89 attenuated IL-1β-induced suppression of promoter activity and endogenous ABCA1 expression. Representative immunoblotting showed that IL-1β enhanced p38 MAPK phosphorylation, whereas SB203580 attenuated this response. IL-1β reduced nuclear PREB expression, and p38 MAPK inhibition restored nuclear PREB expression. Mutation of the PREB-binding site or PREB knockdown abolished IL-1β-mediated suppression of ABCA1 expression. IL-1β also increased intracellular cholesterol content and Oil Red O-positive lipid accumulation. These findings suggest that IL-1β suppresses hepatic ABCA1 expression through p38 MAPK signaling and an H-89-sensitive pathway, at least partly involving PREB-associated transcriptional regulation, and that this suppression is associated with hepatocellular lipid accumulation.",
  "abstract_shown": true,
  "affiliations": [],
  "article_type": null,
  "arxiv": null,
  "author_total": 15,
  "authors": [
    {
      "name": "Jingya Lyu"
    },
    {
      "name": "Kensaku Fukunaga"
    },
    {
      "name": "Zhangchi He"
    },
    {
      "name": "Hitomi Imachi"
    },
    {
      "name": "Toshihiro Kobayashi"
    },
    {
      "name": "Takanobu Saheki"
    },
    {
      "name": "Takafumi Yoshimura"
    },
    {
      "name": "Eri Harada"
    },
    {
      "name": "Kosuke Izumi"
    },
    {
      "name": "Wenyi Jiang"
    },
    {
      "name": "Haotian Zhang"
    },
    {
      "name": "Ly Rathana"
    },
    {
      "name": "Hisakazu Iwama"
    },
    {
      "name": "Jinghui Guo"
    },
    {
      "name": "Koji Murao"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/6ptne354fcqm4.bib",
  "cited_by": 0,
  "doi": "10.1507/endocrj.ej26-0223",
  "fulltext_url": "https://www.jstage.jst.go.jp/article/endocrj/advpub/0/advpub_EJ26-0223/_article",
  "id": "6ptne354fcqm4",
  "issns": [
    "1348-4540",
    "0918-8959"
  ],
  "landing_url": "https://www.jstage.jst.go.jp/article/endocrj/advpub/0/advpub_EJ26-0223/_article",
  "language": null,
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "jstage-journal",
      "medicine/endocrinology-metabolism"
    ],
    [
      "openalex",
      "2746|Cholesterol and Lipid Metabolism"
    ]
  ],
  "openalex": "W7204090021",
  "pdf_url": "https://www.jstage.jst.go.jp/article/endocrj/advpub/0/advpub_EJ26-0223/_pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-08-25",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/6ptne354fcqm4.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:20Z",
      "native_id": "10.1507/endocrj.ej26-0223",
      "source": "jstage",
      "url": "https://www.jstage.jst.go.jp/article/endocrj/advpub/0/advpub_EJ26-0223/_article"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2746|Cholesterol and Lipid Metabolism",
      "subfield": "surgery"
    }
  ],
  "title": "Interleukin-1β decreases hepatic ATP-binding cassette subfamily A member 1 expression through p38 mitogen-activated protein kinase signaling and an H-89-sensitive pathway",
  "title_text": "Interleukin-1β decreases hepatic ATP-binding cassette subfamily A member 1 expression through p38 mitogen-activated protein kinase signaling and an H-89-sensitive pathway",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:17:20Z",
  "url": "https://research.draconitic.com/paper/6ptne354fcqm4",
  "venue": "Endocrine Journal",
  "versions": []
}