{
  "abstract": "The colonic epithelial barrier is a multilayered defense system comprising the mucus layer, intestinal epithelial cells (IECs), and the underlying lamina propria. These components collectively maintain mucosal homeostasis and restrict microbial translocation. Disruption of this barrier is a hallmark of chronic intestinal inflammation particularly in IBDs, and is primarily driven by pro-inflammatory cytokines, such as TNF-α, IFN-γ, IL-1β, and IL-6. TNF-α and IFN-γ synergistically induce epithelial cell apoptosis and tight junction disassembly through mechanisms involving TNFR2 upregulation, myosin light chain kinase (MLCK) activation, and adherens junction destabilization. IL-1β amplifies paracellular permeability via NF-κB-dependent MLCK induction and OCLN downregulation, while IL-6 promotes barrier leakiness by upregulating CLDN-2 and sustaining self-reinforcing inflammatory loops that maintain chronic inflammation and impede epithelial repair. This leads to persistent immune-cell infiltration, chronic tight junction remodeling, and failure of barrier replenishment. Consequently, leaky colon facilitates microbial and antigen translocation into the lamina propria, further activating immune cells and perpetuating pro-inflammatory signaling. This review synthesizes current evidence and studies on the cooperative and self-reinforcing roles of pro-inflammatory cytokines, providing insight into the mechanisms underlying chronic intestinal barrier dysfunction and highlighting the need for therapeutic strategies that simultaneously target multiple inflammatory axes to restore barrier integrity in inflammatory bowel disorders.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Tissue Engineering and Regenerative Medicine, Faculty of Medicine, Universiti Kebangsaan Malaysia, Cheras 56000, Malaysia",
    "Department of Biochemistry, Faculty of Medicine, Universiti Kebangsaan Malaysia, Cheras 56000, Malaysia",
    "International Medical School, Management and Science University, Shah Alam 40100, Malaysia",
    "Department of Physiology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Cheras 56000, Malaysia"
  ],
  "article_type": "review",
  "arxiv": null,
  "author_total": 6,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Dinesh Prasad V Thanga Velu",
      "orcid": "0009-0000-5171-7907"
    },
    {
      "affs": [
        0
      ],
      "name": "Mh Busra Fauzi",
      "orcid": "0000-0001-6449-639X"
    },
    {
      "affs": [
        1
      ],
      "name": "Faizul Jaafar",
      "orcid": "0000-0001-8334-6821"
    },
    {
      "affs": [
        2
      ],
      "name": "Norfilza Mohd Mokhtar",
      "orcid": "0000-0002-4863-100X"
    },
    {
      "affs": [
        3
      ],
      "name": "Mohd Helmy Mokhtar",
      "orcid": "0000-0002-7801-6358"
    },
    {
      "affs": [
        3
      ],
      "name": "Adila A. Hamid",
      "orcid": "0000-0002-1330-4607"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/c0gk539cyqz9t.bib",
  "cited_by": 8,
  "doi": "10.3390/ijms27114722",
  "fulltext_url": null,
  "id": "c0gk539cyqz9t",
  "issns": [
    "1422-0067",
    "1661-6596"
  ],
  "landing_url": "https://doi.org/10.3390/ijms27114722",
  "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": [
    [
      "openalex",
      "1311|Inflammatory Bowel Disease"
    ]
  ],
  "openalex": "W7162255391",
  "pdf_url": null,
  "pmcid": "PMC13257385",
  "pmid": "42278255",
  "published": "2026-05-24",
  "publisher": "Multidisciplinary Digital Publishing Institute",
  "ris": "https://research.draconitic.com/paper/c0gk539cyqz9t.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T13:26:48Z",
      "native_id": "W7162255391",
      "source": "openalex",
      "url": "https://doi.org/10.3390/ijms27114722"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:1311|Inflammatory Bowel Disease",
      "subfield": "genetics-genomics"
    }
  ],
  "title": "Pro-Inflammatory Cytokines as Core Mediators of Colonic Epithelial Barrier Dysfunction: Roles of TNF-α, IFN-γ, IL-1β, and IL-6",
  "title_text": "Pro-Inflammatory Cytokines as Core Mediators of Colonic Epithelial Barrier Dysfunction: Roles of TNF-α, IFN-γ, IL-1β, and IL-6",
  "type": "peer-reviewed",
  "updated_at": "2026-11-04T13:21:07Z",
  "url": "https://research.draconitic.com/paper/c0gk539cyqz9t",
  "venue": "International Journal of Molecular Sciences",
  "versions": []
}