ArticleMucosal immunology2014
Contribution of epithelial innate immunity to systemic protection afforded by prolyl hydroxylase inhibition in murine colitis.
Article in Mucosal immunology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 71 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
71 citing papers in PubMed, 109 citations in OpenAlex.
- Randomised clinical trial: a phase 1b study of GB004, an oral HIF-1α stabiliser, for treatment of ulcerative colitis.Alimentary pharmacology & therapeutics · 2022Trial
- Iron Prevents Hypoxia-Associated Inflammation Through the Regulation of Nuclear Factor-κB in the Intestinal Epithelium.Cellular and molecular gastroenterology and hepatology · 2019Trial
- Molecular subtyping and immune microenvironment heterogeneity in pediatric influenza-associated prolonged multiple organ dysfunction syndrome.Translational pediatrics · 2026Article
- HIF-2α-dependent induction of miR-29a restrains TNature communications · 2024Article
- Targeting hypoxia-inducible factors: therapeutic opportunities and challenges.Nature reviews. Drug discovery · 2024Review
- Fundamental role for the creatine kinase pathway in protection from murine colitis.Mucosal immunology · 2023Article
- Article
- Role of HIF1α and HIF2α in Cre Recombinase-Induced Retinal Pigment Epithelium Pathology and Its Secondary Effect on Choroidal Neovascularization.The American journal of pathology · 2023Article
- The impact of hypoxia-inducible factors in the pathogenesis of kidney diseases: a link through cell metabolism.Kidney research and clinical practice · 2023Article
- Therapeutic Effects and Molecular Mechanism of Chlorogenic Acid on Polycystic Ovarian Syndrome: Role of HIF-1alpha.Nutrients · 2023Review
- Bacterial Lysate from the Multi-Strain Probiotic SLAB51 Triggers Adaptative Responses to Hypoxia in Human Caco-2 Intestinal Epithelial Cells under Normoxic Conditions and Attenuates LPS-Induced Inflammatory Response.International journal of molecular sciences · 2023Article
- Hypoxia and Intestinal Inflammation: Common Molecular Mechanisms and Signaling Pathways.International journal of molecular sciences · 2023Review
- Intelectin-1 binds and alters the localization of the mucus barrier-modifying bacterium Akkermansia muciniphila.The Journal of experimental medicine · 2023Article
- Hypoxia inducible factor prolyl hydroxylases in inflammatory bowel disease.Frontiers in pharmacology · 2023Review
- Hypoxia-Inducible Factor 1-Alpha Stabilizers in the Treatment of Inflammatory Bowel Diseases: Oxygen as a Novel IBD Therapy?Journal of Crohn's & colitis · 2022Review
- Hypoxia-inducible factor as a bridge between healthy barrier function, wound healing, and fibrosis.American journal of physiology. Cell physiology · 2022Review
- Inhibition of hypoxia-inducible factor-prolyl hydroxylation protects from cyclophosphamide-induced bladder injury and urinary dysfunction.American journal of physiology. Renal physiology · 2022Article
- Pathophysiological Concepts and Management of Pulmonary Manifestation of Pediatric Inflammatory Bowel Disease.International journal of molecular sciences · 2022Review
- Eosinophils, Hypoxia-Inducible Factors, and Barrier Dysfunction in Functional Dyspepsia.Frontiers in allergy · 2022Review
- Roxadustat, a Hypoxia-Inducible Factor 1α Activator, Attenuates Both Long- and Short-Term Alcohol-Induced Alcoholic Liver Disease.Frontiers in pharmacology · 2022Article
11 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 3 countries.
Funding
Abstract
Pharmacological stabilization of hypoxia-inducible factor (HIF) through prolyl hydroxylase (PHD) inhibition limits mucosal damage associated with models of murine colitis. However, little is known about how PHD inhibitors (PHDi) influence systemic immune function during mucosal inflammation or the relative importance of immunological changes to mucosal protection. We hypothesized that PHDi enhances systemic innate immune responses to colitis-associated bacteremia. Mice with colitis induced by trinitrobenzene sulfonic acid were treated with AKB-4924, a new HIF-1 isoform-predominant PHDi, and clinical, immunological, and biochemical endpoints were assessed. Administration of AKB-4924 led to significantly reduced weight loss and disease activity compared with vehicle controls. Treated groups were pyrexic but did not become subsequently hypothermic. PHDi treatment augmented epithelial barrier function and led to an approximately 50-fold reduction in serum endotoxin during colitis. AKB-4924 also decreased cytokines involved in pyrogenesis and hypothermia, significantly reducing serum levels of interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α while increasing IL-10. Treatment offered no protection against colitis in epithelial-specific HIF-1α-deficient mice, strongly implicating epithelial HIF-1α as the tissue target for AKB-4924-mediated protection. Taken together, these results indicate that inhibition of prolyl hydroxylase with AKB-4924 enhances innate immunity and identifies that the epithelium is a central site of inflammatory protection afforded by PHDi in murine colitis.
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Registered trials
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.