The synthetic liver X receptor agonist GW3965 reduces tissue factor production and inflammatory responses in human islets in vitro

Autor: Ole Korsgren, Hanne Scholz, Jacob E Wang, Maria K Dahle, Aksel Foss, Jon L. Collins, Tormod Lund
Rok vydání: 2009
Předmět:
Lipopolysaccharides
Male
Benzylamines
endocrine system diseases
Endocrinology
Diabetes and Metabolism
medicine.medical_treatment
Anti-Inflammatory Agents
Cell Culture Techniques
Islets of Langerhans Transplantation
Gene Expression
Receptors
Cytoplasmic and Nuclear
Benzoates
Insulin Secretion
Homeostasis
Insulin
Chemokine CCL2
Liver X Receptors
geography.geographical_feature_category
Islet
Orphan Nuclear Receptors
Tissue Donors
DNA-Binding Proteins
medicine.anatomical_structure
Cholesterol
Female
Agonist
Adult
endocrine system
medicine.medical_specialty
medicine.drug_class
Cell Survival
Biology
Methylprednisolone
Thromboplastin
Tissue factor
Islets of Langerhans
Internal medicine
Internal Medicine
medicine
Humans
Liver X receptor
Aged
geography
Monocyte
Pancreatic islets
Interleukin-8
Transplantation
Endocrinology
Biomarkers
Zdroj: Diabetologia. 52(7)
ISSN: 1432-0428
Popis: Optimising islet culture conditions may be one strategy for reducing islet loss prior to, and immediately after, islet transplantation. Liver X receptor (LXR) agonism has previously been shown to increase insulin release from pancreatic islets and reduce inflammation in leucocytes. Our aim was to investigate whether the synthetic LXR agonist GW3965 could modulate the inflammatory status of human pancreatic islets.Levels of pro-inflammatory cytokines and tissue factor in isolated human islets were determined by TaqMan low density array and/or real-time quantitative RT-PCR (mRNA levels) and enzyme immunoassay (EIA) (protein levels). Islet viability was measured using intracellular ATP content, ADP/ATP ratio, mitochondrial dehydrogenase activity (XTT assay) and insulin secretion in a dynamic glucose-challenge model. Apoptosis was determined by EIA measurement of histone-DNA complexes present in cytoplasm and by assaying caspase-3/-7 activity.Treatment of LPS-stimulated human islets with the synthetic LXR agonist GW3965 (1 micromol/l) for 24 h reduced mRNA and protein levels of selected pro-inflammatory cytokines (IL-8, monocyte chemotactic protein-1 and tissue factor). Moreover, GW3965 had no adverse effect on insulin secretion, islet viability or apoptosis. No excess of lipid accumulation could be detected with the dosage and exposure time used.LXR activation suppresses inflammation in human islets in vitro without adverse effects on islet viability. Short-term moderate activation of LXR prior to islet transplantation may represent a possible strategy for improving post-transplant islet survival.
Databáze: OpenAIRE
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