Carbon Monoxide–Releasing Molecule‐A1 Inhibits Th1/Th17 and Stimulates Th2 Differentiation In vitro

• Published in: Scandinavian journal of immunology 2014-08, Vol.80 (2), p.95-100
• Main Authors: Nikolic, I., Vujicic, M., Stojanovic, I., Stosic‐Grujicic, S., Saksida, T.
• Format: Article
• Language: English
• Subjects: Animals; Antibodies - immunology; Apoptosis - drug effects; Apoptosis - immunology; Boranes - pharmacology; Carbon Monoxide - pharmacology; Carbonates - pharmacology; CD28 Antigens - immunology; CD3 Complex - immunology; Cell Differentiation - drug effects; Cell Differentiation - immunology; Cell Proliferation - drug effects; Cell Survival - drug effects; Cells, Cultured; GATA3 Transcription Factor - biosynthesis; Heme Oxygenase-1 - metabolism; Inflammation - immunology; Interferon-gamma - secretion; Interleukin-17 - secretion; Interleukin-2 Receptor alpha Subunit - biosynthesis; Interleukin-2 Receptor alpha Subunit - immunology; Interleukin-4 - secretion; Lymph Nodes - cytology; Lymph Nodes - drug effects; Lymph Nodes - immunology; Lymphocyte Activation - drug effects; Lymphocyte Activation - immunology; Mice; Mice, Inbred C57BL; Nuclear Receptor Subfamily 1, Group F, Member 3 - biosynthesis; T-Box Domain Proteins - biosynthesis; Th1 Cells - drug effects; Th1 Cells - immunology; Th17 Cells - drug effects; Th17 Cells - immunology; Th2 Cells - drug effects; Th2 Cells - immunology
• ISSN: 0300-9475; 1365-3083
• DOI: 10.1111/sji.12189

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‐γ and IL‐17, while the secretion of anti‐inflammatory cytokine IL‐4 remained unchanged. Furthermore, CORM‐A1 efficiently reduced the percentage of CD4+IFN‐γ+ and CD4+IL‐17+ cells, whereas CD4+IL‐4+ cell population increased after treatment. Also, CORM‐A1 significantly reduced expression of transcription factor RORγT, 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.