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Tissue factor produced by the endocrine cells of the islets of Langerhans is associated with a negative outcome of clinical islet transplantation. The impact of short-term ciclosporin A treatment on insulin secretion and insulin sensitivity in man. The ADP/ATP ratio: A novel predictive assay for quality assessment of isolated pancreatic islets.Ĭalcineurin/NFAT signalling regulates pancreatic beta-cell growth and function.Īn endogenous regulator of inflammation, resolvin E1, modulates osteoclast differentiation and bone resorption. Refinement of the automated method for human islet isolation and presentation of a closed system for in vitro islet culture. Positron emission tomography: a real-time tool to quantify early islet engraftment in a preclinical large animal model. Visualization of early engraftment in clinical islet transplantation by positron-emission tomography. Resolvin E1, an EPA-derived mediator in whole blood, selectively counterregulates leukocytes and platelets. Resolvin E1 promotes mucosal surface clearance of neutrophils: a new paradigm for inflammatory resolution. Measurement of the ADP:ATP ratio in human leukaemic cell lines can be used as an indicator of cell viability, necrosis and apoptosis.Ĭampbell EL, Louis NA, Tomassetti SE. Incompatibility between human blood and isolated islets of Langerhans: a finding with implications for clinical intraportal islet transplantation?.īradbury DA, Simmons TD, Slater KJ. Inflammation-mediated dysfunction and apoptosis in pancreatic islet transplantation: implications for intrahepatic grafts. Molecular circuits of resolution: formation and actions of resolvins and protectins. Lipoxins and novel 15-epi-lipoxin analogs display potent anti-inflammatory actions after oral administration.īannenberg GL, Chiang N, Ariel A. Resolvin E1, an endogenous lipid mediator derived from omega-3 eicosapentaenoic acid, protects against 2,4,6-trinitrobenzene sulfonic acid-induced colitis.īannenberg G, Moussignac RL, Gronert K. Resolvin E1 selectively interacts with leukotriene B4 receptor BLT1 and ChemR23 to regulate inflammation. Stereochemical assignment, antiinflammatory properties, and receptor for the omega-3 lipid mediator resolvin E1. Islet - transplantation - resolvin - cytokine - IBMIR ReferencesĪrita M, Bianchini F, Aliberti J. We conclude that RvE1 may have potential in clinical islet transplantation. Additionally, RvE1 has modest dampening effects on IBMIR. RvE1 demonstrates anti-apoptotic effects in a proinflammatory milieu. Additionally, RvE1 reduced platelet consumption and TAT complex formation during the first 5 min after islet-blood contact.Ĭonclusions: RvE1 suppresses proinflammatory markers and lowers the ADP/ATP ratio in human islets in vitro. RvE1 reduced the apoptotic effect of proinflammatory cytokines. RvE1 lowered the ADP/ATP ratio, but had no effect on insulin secretion. Results: Treatment of human islets with RvE1 (500 nM) for 24 h reduced LPS-induced increase in mRNA and protein levels of selected pro-inflammatory markers (IL-8, MCP-1, and TF). To assess effect on IBMIR, human islets were mixed with non-anticoagulated, RvE1 or vehicle pretreated ABO-compatible blood in heparin-coated tubing loops. Apoptosis was measured using commercial kits after stimulation with proinflammatory cytokines.
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Islet viability was measured using insulin secretion in a dynamic model, ADP/ATP ratio and total ATP content. Methods: Pro-inflammatory cytokines and tissue factor (TF) in isolated human islets were determined by real-time RT-qPCR (mRNA levels), CBA and Gyrolab bioaffy (protein levels) after lipopolysaccaride (LPS) stimulation. We investigated the effect of RvE1 on i) the inflammatory status of human pancreatic islets, ii) islet viability and apoptosis, and iii) the instant blood-mediated inflammatory reaction (IBMIR) in vitro. The resolution of acute inflammation is an active process mediated by specific signals and mediators such as resolvin E1 (RvE1).
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Buy Article Permissions and Reprints Abstractīackground: In clinical islet transplantation, inflammatory responses initiated by the transplanted islets and by the host immune system cause acute and chronic graft loss.