ArticlePloS one2014
Pro-inflammatory and pro-oxidant status of pancreatic islet in vitro is controlled by TLR-4 and HO-1 pathways.
Article in PloS one, 2014. 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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Who cites it
18 citing papers in PubMed, 33 citations in OpenAlex.
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- Enhancing the Functionality of Immunoisolated Human SC-βeta Cell Clusters through Prior Resizing.Small (Weinheim an der Bergstrasse, Germany) · 2024Article
- Interplay of Environmental, Individual and Genetic Factors in Rheumatoid Arthritis Provocation.International journal of molecular sciences · 2022Review
- Comprehensive analysis of gene expression of isolated pancreatic islets during pretransplant culture.Fukushima journal of medical science · 2021Article
- Toll-like Receptors as a Potential Drug Target for Diabetes Mellitus and Diabetes-associated Complications.Diabetes, metabolic syndrome and obesity : targets and therapy · 2020Review
- Therapy to Obese Type 2 Diabetes Mellitus: How Far Will We Go Down the Wrong Road?Chinese journal of integrative medicine · 2020Review
- Differential expression and release of exosomal miRNAs by human islets under inflammatory and hypoxic stress.Diabetologia · 2019Article
- Human mesenchymal stem cells improve rat islet functionality under cytokine stress with combined upregulation of heme oxygenase-1 and ferritin.Stem cell research & therapy · 2019Article
- Improvement of islet graft function using liraglutide is correlated with its anti-inflammatory properties.British journal of pharmacology · 2016Article
- High mobility group box1 protein is involved in acute inflammation induced by Clostridium difficile toxin A.Acta biochimica et biophysica Sinica · 2016Article
- Trimetazidine prevents macrophage-mediated septic myocardial dysfunction via activation of the histone deacetylase sirtuin 1.British journal of pharmacology · 2016Article
- Translational Significance of Heme Oxygenase in Obesity and Metabolic Syndrome.Trends in pharmacological sciences · 2016Review
- Impact of Pancreatic Rat Islet Density on Cell Survival during Hypoxia.Journal of diabetes research · 2016Article
- Fasudil hydrochloride, a potent ROCK inhibitor, inhibits corneal neovascularization after alkali burns in mice.Molecular vision · 2015Article
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Since their isolation until implantation, pancreatic islets suffer a major stress leading to the activation of inflammatory reactions. The maintenance of controlled inflammation is essential to preserve survival and function of the graft. Identification and targeting of pathway(s) implicated in post-transplant detrimental inflammatory events, is mandatory to improve islet transplantation success. We sought to characterize the expression of the pro-inflammatory and pro-oxidant mediators during islet culture with a focus on Heme oxygenase (HO-1) and Toll-like receptors-4 signaling pathways. Rat pancreatic islets were isolated and pro-inflammatory and pro-oxidant status were evaluated after 0, 12, 24 and 48 hours of culture through TLR-4, HO-1 and cyclooxygenase-2 (COX-2) expression, CCL-2 and IL-6 secretion, ROS (Reactive Oxygen Species) production (Dihydroethidine staining, DHE) and macrophages migration. To identify the therapeutic target, TLR4 inhibition (CLI-095) and HO-1 activation (cobalt protoporphyrin,CoPP) was performed. Activation of NFκB signaling pathway was also investigated. After isolation and during culture, pancreatic islet exhibited a proinflammatory and prooxidant status (increase levels of TLR-4, COX-2, CCL-2, IL-6, and ROS). Activation of HO-1 or inhibition of TLR-4 decreased inflammatory status and oxidative stress of islets. Moreover, the overexpression of HO-1 induced NFκB phosphorylation while the inhibition of TLR-4 had no effect NFκB activation. Finally, inhibition of pro-inflammatory pathway induced a reduction of macrophages migration. These data demonstrated that the TLR-4 signaling pathway is implicated in early inflammatory events leading to a pro-inflammatory and pro-oxidant status of islets in vitro. Moreover, these results provide the mechanism whereby the benefits of HO-1 target in TLR-4 signaling pathway. HO-1 could be then an interesting target to protect islets before transplantation.
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