Anti-diabetic actions of carbon monoxide-releasing molecule (CORM)-A1: Immunomodulation and regeneration of islet beta cells
2015
Аутори:
Nikolić, IvanaSaksida, Tamara
Vujičić, Milica
Stojanović, Ivana D.
Stošić-Grujičić, Stanislava
Тип документа:
Чланак у часопису (Објављена верзија)
Метаподаци
Приказ свих података о документуАпстракт:
We have recently shown that carbon monoxide releasing molecule (CORM)-A1
prevents type 1 diabetes induced in C57BL/6 mice with multiple low doses
of streptozotocin (MLDS) by shifting the Th1/Th17/M1 balance towards a
Th2/M2 response. In the present work we tested the hypothesis that
CORM-A1 might influence regulatory arm of the immune response, as well
as beta cell regeneration. CORM-A1 (2 mg/kg/day) was administered for 10
days to mice induced with MLDS and/or depleted of low dose
cyclophosphamide (CY)-sensitive FoxP3(+) T regulatory (Treg) cells.
Besides monitoring hyperglycaemia, ex vivo analysis of spleen,
pancreatic lymph nodes (PLN) and pancreas was performed at the end of
treatment. In CORM-A1-treated MLDS-induced mice the improvement of
hyperglycaemia was observed only without depletion of CY-sensitive
FoxP3(+) Treg cells. This was accompanied by decreased levels of
interleukin (IL)-12, IL-2 and early activation marker CD25 in the spleen
and PLN and increased transforming growth factor (TGF)-beta, resulting
in reduced lymphocyte proliferation in both organs. In parallel,
decreased transcript levels of IL-2, but increased mRNA expression of
TGF-beta, accompanied with up-regulation of Ki-67 protein expression was
observed within pancreas. Together, the data suggested that besides the
immunomodulatory potential, CORM-A1 probably induces beta cell
regeneration. (C) 2015 European Federation of Immunological Societies.
Published by Elsevier B.V. All rights reserved.
Кључне речи:
Carbon monoxide-releasing molecule A1; Lymphocytes; Cytokines; Islets of Langerhans; Type 1 diabetesИзвор:
Immunology Letters, 2015, 165, 1, 39-46
DOI: 10.1016/j.imlet.2015.03.009
ISSN: 1879-0542