ArticleGastroenterology2018
Pyrin Inflammasome Regulates Tight Junction Integrity to Restrict Colitis and Tumorigenesis.
Article in Gastroenterology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 108 papers.
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Who cites it
108 citing papers in PubMed, 157 citations in OpenAlex.
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- Towards a basis for vascular versus intestinal phenotype differences; East Meets West in Behcet's disease.Frontiers in immunology · 2026Review
- Gastrointestinal microbiota and inflammasomes interplay in health and disease: a gut feeling.Gut · 2025Review
- The Significance of STAT3 in Colonic Diseases: A Comprehensive Study of Pathological Roles and Therapeutic Implications.Cell biochemistry and biophysics · 2025Review
- Molecular mechanisms and regulation of inflammasome activation and signaling: sensing of pathogens and damage molecular patterns.Cellular & molecular immunology · 2025Review
- Harnessing gut microbiota for colorectal cancer therapy: from clinical insights to therapeutic innovations.NPJ biofilms and microbiomes · 2025Review
- Natural compounds and programmed necrosis: pioneering a new frontier in cancer treatments.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- NLRP3 promotes NK cell-mediated cytotoxicity and inhibits colorectal cancer development via the NKG2D signaling pathway.Journal of molecular histology · 2025Article
- The interplay between host immunity andmBio · 2025Review
- FXR acts as a therapeutic target for ulcerative colitis via suppressing ferroptosis.Molecular medicine (Cambridge, Mass.) · 2025Article
- Qingjie Fuzheng Granule prevents colitis-associated colorectal cancer by inhibiting abnormal activation of NOD2/NF-Chinese herbal medicines · 2025Article
- Medicinal Mushrooms in Colon Cancer Therapy: Mechanisms of Action of Bioactive Compounds and Therapeutic Potential.International journal of molecular sciences · 2025Review
- Familial Mediterranean fever with sigmoid colon stricture.Clinical journal of gastroenterology · 2025Article
- The Role of the Tumor Microenvironment (TME) in Advancing Cancer Therapies: Immune System Interactions, Tumor-Infiltrating Lymphocytes (TILs), and the Role of Exosomes and Inflammasomes.International journal of molecular sciences · 2025Review
- Dietary supplementation with milk-derivediMetaOmics · 2025Article
48 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
BACKGROUND &
aimsInflammatory bowel diseases (IBD) increase risk for colorectal cancer. Mutations in the Mediterranean fever gene (MEFV or pyrin) are associated with hereditary autoinflammatory disease and severe IBD. Expression of MEFV, a sensor protein that the initiates assembly of the inflammasome complex, is increased in colon biopsies from patients with IBD. We investigated the role of pyrin in intestinal homeostasis in mice.
methodsMefv
resultsMEFV was expressed in colons of control mice and expression increased during chronic and acute inflammation; high levels were detected in colon tumor and adjacent non-tumor tissues. Mefv-/- mice developed more severe colitis than control mice, with a greater extent of epithelial hyperplasia and a larger tumor burden. Levels of inflammatory cytokines (IL6) and chemokines were significantly higher in colons of Mefv-/- mice than control mice following colitis induction, whereas the level IL18, which depends on the inflammasome for maturation and release, was significantly lower in colons of Mefv-/- mice. Mefv-/- mice had increased epithelial permeability following administration of DSS than control mice, and loss of the tight junction proteins occludin and claudin-2 from intercellular junctions. STAT3 was activated (phosphorylated) in inflamed colon tissues from Mefv-/-, which also had increased expression of stem cell markers (OLFM4, BMI1, and MSI1) compared with colons from control mice. Administration of rIL18 to Mefv-/- mice reduced epithelial permeability, intestinal inflammation, the severity of colitis, and colon tumorigenesis.
conclusionsIn studies with DSS-induced colitis, we found that pyrin (MEFV) is required for inflammasome activation and IL18 maturation, which promote intestinal barrier integrity and prevent colon inflammation and tumorigenesis. Strategies to increase activity of MEFV or IL18 might be developed for the treatment of IBD and prevention of colitis-associated tumorigenesis.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.