ArticleCell transplantation2017
Physiologic Doses of Bilirubin Contribute to Tolerance of Islet Transplants by Suppressing the Innate Immune Response.
Article in Cell transplantation, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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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
18 citing papers in PubMed, 33 citations in OpenAlex.
- Bilirubin in Parkinson's disease: pathogenic mechanisms and therapeutic potentials.Frontiers in neuroscience · 2026Review
- Bilirubin - new insights into an old molecule.Biochemia medica · 2025Review
- Bilirubin Levels in Infancy and Their Associations with Body Weight, Levels of Iron-Related Parameters and Steroid Hormone Levels.Metabolites · 2024Article
- Anti-Oxidative Therapy in Islet Cell Transplantation.Antioxidants (Basel, Switzerland) · 2022Review
- Bilirubin as a Therapeutic Molecule: Challenges and Opportunities.Antioxidants (Basel, Switzerland) · 2021Review
- Life-Long Hyperbilirubinemia Exposure and Bilirubin Priming PreventFrontiers in pharmacology · 2021Article
- Heme Degradation in Pathophysiology of and Countermeasures to Inflammation-Associated Disease.International journal of molecular sciences · 2020Review
- Modulation of Inflammation and Immune Responses by Heme Oxygenase-1: Implications for Infection with Intracellular Pathogens.Antioxidants (Basel, Switzerland) · 2020Review
- Engineering Strategies to Improve Islet Transplantation for Type 1 Diabetes Therapy.ACS biomaterials science & engineering · 2020Article
- Two Faces of Heme Catabolic Pathway in Newborns: A Potential Role of Bilirubin and Carbon Monoxide in Neonatal Inflammatory Diseases.Oxidative medicine and cellular longevity · 2020Review
- Bilirubin Protects Transplanted Islets by Targeting Ferroptosis.Frontiers in pharmacology · 2020Article
- Heme-Derived Metabolic Signals Dictate Immune Responses.Frontiers in immunology · 2020Review
- Heme Oxygenase Dependent Bilirubin Generation in Vascular Cells: A Role in Preventing Endothelial Dysfunction in Local Tissue Microenvironment?Frontiers in physiology · 2020Review
- Hyperbilirubinemia in Gunn Rats is Associated with Decreased Inflammatory Response in LPS-Mediated Systemic Inflammation.International journal of molecular sciences · 2019Article
- Heme Catabolic Pathway in Inflammation and Immune Disorders.Frontiers in pharmacology · 2019Review
- Selective Osmotic Shock for Islet Isolation in the Cadaveric Canine Pancreas.Cell transplantation · 2018Article
- Nano-Encapsulation of Bilirubin in Pluronic F127-Chitosan Improves Uptake in β Cells and Increases Islet Viability and Function after Hypoxic Stress.Cell transplantation · 2017Article
- In Vitro Evaluation of a Novel Synthetic Bilirubin Analog as an Antioxidant and Cytoprotective Agent for Pancreatic Islet Transplantation.Cell transplantationArticle
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
Bilirubin has been recognized as a powerful cytoprotectant when used at physiologic doses and was recently shown to have immunomodulatory effects in islet allograft transplantation, conveying donor-specific tolerance in a murine model. We hypothesized that bilirubin, an antioxidant, acts to suppress the innate immune response to islet allografts through two mechanisms: 1) by suppressing graft release of damage-associated molecular patterns (DAMPs) and inflammatory cytokines, and 2) by producing a tolerogenic phenotype in antigen-presenting cells. Bilirubin was administered intraperitoneally before pancreatic procurement or was added to culture media after islet isolation in AJ mice. Islets were exposed to transplant-associated nutrient deprivation and hypoxia. Bilirubin significantly decreased islet cell death after isolation and hypoxic stress. Bilirubin supplementation of islet media also decreased the release of DAMPs (HMGB1), inflammatory cytokines (IL-1β and IL-6), and chemokines (MCP-1). Cytoprotection was mediated by the antioxidant effects of bilirubin. Treatment of macrophages with bilirubin induced a regulatory phenotype, with increased expression of PD-L1. Coculture of these macrophages with splenocytes led to expansion of Foxp3+ Tregs. In conclusion, exogenous bilirubin supplementation showed cytoprotective and antioxidant effects in a relevant model of islet isolation and hypoxic stress. Suppression of DAMP release, alterations in cytokine profiles, and tolerogenic effects on macrophages suggest that the use of this natural antioxidant may provide a method of preconditioning to improve outcomes after allograft transplantation.
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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.