Carbon Monoxide-Releasing Molecule-A1 Inhibits Th1/Th17 and Stimulates Th2 Differentiation In vitro
2014
Аутори:
Nikolić, IvanaVujičić, Milica
Stojanović, Ivana D.
Stošić-Grujičić, Stanislava
Saksida, Tamara
Тип документа:
Чланак у часопису (Објављена верзија)
Метаподаци
Приказ свих података о документуАпстракт:
Carbon monoxide (CO) is endogenously produced by haeme oxygenase-1 and
has profound effects on intracellular signalling processes, generating
anti-inflammatory, antiproliferative and antiapoptotic effects. A
boron-containing compound CORM-A1 is capable of releasing CO in such a
way to mimic physiological functions of haeme oxygenase-1. Considering
the importance of Th1/Th17 versus Th2 balance in the final outcome of
immune and inflammatory responses in this study we focused on
immune-modulatory effects of CORM-A1 on murine lymph node-derived T
cells in vitro and its influence on T-cell proliferation, activation and
differentiation. Anti-CD3/CD28 antibody-triggered lymph node cells
proliferation remained unaffected after 24-hour CORM-A1 treatment, as
well as the expression of the early activation marker CD25. However,
CORM-A1 successfully reduced the secretion of the two representative
pro-inflammatory cytokines, IFN-gamma and IL-17, while the secretion of
anti-inflammatory cytokine IL-4 remained unchanged. Furthermore, CORM-A1
efficiently reduced the percentage of CD4(+)IFN-gamma(+) and
CD4(+)IL-17(+) cells, whereas CD4(+)IL-4(+) cell population increased
after treatment. Also, CORM-A1 significantly reduced expression of
transcription factor ROR gamma T, necessary for Th17 development, but
the expression of Th1-related and Th2-related transcription factors
(T-bet and GATA-3, respectively) remained unchanged. In conclusion, our
findings indicate that CO has anti-inflammatory role through the
regulation of balance between pro-inflammatory Th1/Th17 and
anti-inflammatory Th2 cells. Observed immunomodulatory effects of
CORM-A1 could be useful for developing novel therapeutic approaches in
managing Th1/Th17-mediated immune disorders.
Извор:
Scandinavian Journal of Immunology, 2014, 80, 2, 95-100
DOI: 10.1111/sji.12189
ISSN: 1365-3083