dc.creator | Nikolić, Ivana | |
dc.creator | Saksida, Tamara | |
dc.creator | Mangano, Katia | |
dc.creator | Vujičić, Milica | |
dc.creator | Stojanović, Ivana D. | |
dc.creator | Nicoletti, Ferdinando | |
dc.creator | Stošić-Grujičić, Stanislava | |
dc.date.accessioned | 2016-05-23T11:00:35Z | |
dc.date.issued | 2014 | |
dc.identifier.issn | 1432-0428 | |
dc.identifier.uri | https://radar.ibiss.bg.ac.rs/handle/123456789/2221 | |
dc.description.abstract | Aims/hypothesis Recent studies have identified carbon monoxide (CO) as a
potential therapeutic molecule for the treatment of autoimmune diseases
owing to its anti-inflammatory and anti-apoptotic properties. We
explored the efficacy and the mechanisms of action of the CO-releasing
molecule (CORM)-A1 in preclinical models of type 1 diabetes.
Methods The impact of CORM-A1 on diabetes development was evaluated in
models of spontaneous diabetes in NOD mice and in diabetes induced in
C57BL/6 mice by multiple low-dose streptozotocin (MLDS). Ex vivo
analysis was performed to determine the impact of CORM-A1 both on T
helper (Th) cell and macrophage differentiation and on their production
of soluble mediators in peripheral tissues and in infiltrates of
pancreatic islets. The potential effect of CORM-A1 on cytokine-induced
apoptosis in pancreatic islets or beta cells was evaluated in vitro.
Results CORM-A1 conferred protection from diabetes in MLDS-induced mice
and reduced diabetes incidence in NOD mice as confirmed by preserved
insulin secretion and improved histological signs of the disease. In
MLDS-challenged mice, CORM-A1 attenuated Th1, Th17, and M1 macrophage
response and facilitated Th2 cell differentiation. In addition, CORM-A1
treatment in NOD mice upregulated the regulatory arm of the immune
response (M2 macrophages and FoxP3(+) regulatory T cells). Importantly,
CORM-A1 interfered with in vitro cytokine-induced beta cell apoptosis
through the reduction of cytochrome c and caspase 3 levels.
Conclusions/interpretation The ability of CORM-A1 to protect mice from
developing type 1 diabetes provides a valuable proof of concept for the
potential exploitation of controlled CO delivery in clinical settings
for the treatment of autoimmune diabetes. | en |
dc.description.sponsorship | European Foundation; Ministry of Education, Science and Technological
Development, Republic of Serbia {[}173013] | |
dc.language | English | |
dc.rights | restrictedAccess | |
dc.source | Diabetologia | |
dc.subject | Beta cell apoptosis | |
dc.subject | Carbon monoxide-releasing | |
dc.subject | molecule-A1 | |
dc.subject | Cytokines | |
dc.subject | Type 1 diabetes | |
dc.title | Pharmacological application of carbon monoxide ameliorates
islet-directed autoimmunity in mice via anti-inflammatory and
anti-apoptotic effects | en |
dc.type | article | |
dc.rights.license | ARR | |
dcterms.abstract | Николић, Ивана; Мангано, Катиа; Ницолетти, Фердинандо; Вујичић, Милица; Стошић-Грујичић, Станислава Д.; Саксида, Тамара; Стојановиц, Ивана; | |
dc.citation.issue | 5 | |
dc.citation.volume | 57 | |
dc.identifier.doi | 10.1007/s00125-014-3170-7 | |
dc.identifier.scopus | 2-s2.0-84898600879 | |
dc.identifier.wos | 000334494700017 | |
dc.citation.spage | 980 | |
dc.citation.epage | 990 | |
dc.type.version | publishedVersion | en |