{
  "abstract": "Introduction: Dysregulation of the pulmonary endothelial barrier precipitates the edema and inflammation central to sepsis-associated acute lung injury (ALI). Although the G-protein-coupled receptor GPR84 orchestrates various inflammatory responses, its specific contribution to maintaining microvascular integrity during sepsis remains largely undefined.\n\nMethods: We explored the therapeutic efficacy of GPR84 inhibition using a cecal ligation and puncture (CLP) mouse model and LPS-challenged lung microvascular endothelial cells (MLMECs).\n\nResults: Pulmonary GPR84 expression surged following septic insult, and its pharmacological blockade via selective inhibitors (GLPG1205 or TUG-2181) effectively mitigated alveolar damage. This intervention restored respiratory mechanics—including peak expiratory flow (PEF) and airway resistance (Raw)—and decreased pro-inflammatory cytokine concentrations (TNF-α, IL-6, CXCL15) within the bronchoalveolar lavage fluid. Furthermore, GPR84 inhibition curtailed vascular protein leakage and preserved Occludin expression across both experimental models. At the molecular level, GPR84 signaling appeared to facilitate the LPS-induced upregulation of the transcription factor YY1. In cultured endothelial cells, the barrier-protective effect of GPR84 inhibition was diminished by YY1 overexpression, indicating a functional role for YY1 in this in vitro system.\n\nDiscussion: Collectively, these results suggest that GPR84 inhibition attenuates sepsis-associated ALI in association with YY1 suppression in vivo, identifying GPR84 as a candidate therapeutic target warranting further preclinical and clinical evaluation.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Critical Care Medicine, The Fifth Affiliated Hospital of Zhengzhou University",
    "Department of Infectious Diseases, The Fifth Affiliated Hospital of Zhengzhou University"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 5,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Mingzhu Wang"
    },
    {
      "affs": [
        1
      ],
      "name": "Huifen Feng"
    },
    {
      "affs": [
        0
      ],
      "name": "Chao Qin"
    },
    {
      "affs": [
        1
      ],
      "name": "Yujie Yin"
    },
    {
      "affs": [
        1
      ],
      "name": "Xuelian Huang"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/9rq7st3g78bpg.bib",
  "cited_by": 0,
  "doi": "10.3389/fphar.2026.1877785",
  "fulltext_url": null,
  "id": "9rq7st3g78bpg",
  "issns": [
    "1663-9812"
  ],
  "landing_url": "https://www.frontiersin.org/articles/10.3389/fphar.2026.1877785/full",
  "language": null,
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2713|Sepsis Diagnosis and Treatment"
    ]
  ],
  "openalex": "W7224137684",
  "pdf_url": "https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2026.1877785/pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-28",
  "publisher": "Frontiers Media SA",
  "ris": "https://research.draconitic.com/paper/9rq7st3g78bpg.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:20:06Z",
      "native_id": "10.3389/fphar.2026.1877785",
      "source": "crossref",
      "url": "https://www.frontiersin.org/articles/10.3389/fphar.2026.1877785/full"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2713|Sepsis Diagnosis and Treatment",
      "subfield": "epidemiology-public-health"
    }
  ],
  "title": "GPR84 inhibition attenuates sepsis-associated acute lung injury and preserves pulmonary endothelial barrier function associated with YY1 suppression",
  "title_text": "GPR84 inhibition attenuates sepsis-associated acute lung injury and preserves pulmonary endothelial barrier function associated with YY1 suppression",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:20:06Z",
  "url": "https://research.draconitic.com/paper/9rq7st3g78bpg",
  "venue": "Frontiers in Pharmacology",
  "versions": []
}