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Carbon Monoxide–Releasing Molecule‐A1 Inhibits Th1/Th17 and Stimulates Th2 Differentiation In vitro
Author(s) -
Nikolic I.,
Vujicic M.,
Stojanovic I.,
StosicGrujicic S.,
Saksida T.
Publication year - 2014
Publication title -
scandinavian journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.934
H-Index - 88
eISSN - 1365-3083
pISSN - 0300-9475
DOI - 10.1111/sji.12189
Subject(s) - cytokine , transcription factor , immune system , chemistry , il 2 receptor , microbiology and biotechnology , rar related orphan receptor gamma , population , immunology , t cell , biology , foxp3 , medicine , biochemistry , gene , environmental health
Abstract 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‐ CD 3/ CD 28 antibody‐triggered lymph node cells proliferation remained unaffected after 24‐hour CORM ‐A1 treatment, as well as the expression of the early activation marker CD 25. However, CORM ‐A1 successfully reduced the secretion of the two representative pro‐inflammatory cytokines, IFN ‐ γ and IL ‐17, while the secretion of anti‐inflammatory cytokine IL ‐4 remained unchanged. Furthermore, CORM ‐A1 efficiently reduced the percentage of CD 4 + IFN ‐ γ + and CD 4 + IL ‐17 + cells, whereas CD 4 + IL ‐4 + cell population increased after treatment. Also, CORM ‐A1 significantly reduced expression of transcription factor ROR γ 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.

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