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Interleukin-22 reverses human islet dysfunction and apoptosis triggered by hyperglycemia and LIGHT
Oslo University Hospital, Oslo, Norway.
Oslo University Hospital, Oslo, Norway.
University of Oslo, Oslo, Norway.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.ORCID iD: 0000-0002-8524-9547
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2018 (English)In: Journal of Molecular Endocrinology, ISSN 0952-5041, E-ISSN 1479-6813, Vol. 60, no 3, p. 171-183Article in journal (Refereed) Published
Abstract [en]

Interleukin (IL)-22 has recently been suggested as an anti-inflammatory cytokine that could protect the islet cells from inflammation- and glucose-induced toxicity. We have previously shown that the tumor necrosis factor family member, LIGHT can impair human islet function at least partly via pro-apoptotic effects. Herein, we aimed to investigate the protective role of IL-22 on human islets exposed to the combination of hyperglycemia and LIGHT. First, we found up-regulation of LIGHT receptors (LTβR and HVEM) in engrafted human islets exposed to hyperglycemia (>11 mM) for 17 days post transplantation by using a double islet transplantation mouse model as well as in human islets cultured with high glucose (HG) (20mM glucose) + LIGHT in vitro and this latter effect was attenuated by IL-22. The effect of HG + LIGHT impairing glucose stimulated insulin secretion was reversed by IL-22. The harmful effect of HG + LIGHT on human islet function seemed to involve enhanced endoplasmic reticulum stress evidenced by up-regulation of p-IRE1α and BiP, elevated secretion of pro-inflammatory cytokines (IL-6, IL-8, IP-10 and MCP-1) and the pro-coagulant mediator tissue factor (TF) release and apoptosis in human islets, whereas all these effects were at least partly reversed by IL-22. Our findings suggest that IL-22 could counteract the harmful effects of LIGHT/hyperglycemia on human islet cells and potentially support the strong protective effect of IL-22 on impaired islet function and survival.

Place, publisher, year, edition, pages
2018. Vol. 60, no 3, p. 171-183
National Category
Endocrinology and Diabetes
Identifiers
URN: urn:nbn:se:uu:diva-342896DOI: 10.1530/JME-17-0182ISI: 000438183300006PubMedID: 29330151OAI: oai:DiVA.org:uu-342896DiVA, id: diva2:1185331
Funder
Novo Nordisk, 36772Swedish Child Diabetes FoundationAvailable from: 2018-02-23 Created: 2018-02-23 Last updated: 2018-09-20Bibliographically approved

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