Dextromethorphan inhibits activations and functions in dendritic cells
Journal
Clinical and Developmental Immunology
Journal Volume
2013
Date Issued
2013
Author(s)
Chen, D.-Y.
Song, P.-S.
Hong, J.-S.
Pan, I.-H.
Chen, Y.-M.
Lin, C.-H.
Lin, S.-H.
Lin, C.-C.
Abstract
Dendritic cells (DCs) play an important role in connecting innate and adaptive immunity. Thus, DCs have been regarded as a major target for the development of immunomodulators. In this study, we examined the effect of dextromethorphan (DXM), a common cough suppressant with a high safety profile, on the activation and function of DCs. In the presence of DXM, the LPS-induced expression of the costimulatory molecules in murine bone marrow-derived dendritic cells (BMDCs) was significantly suppressed. In addition, DXM treatment reduced the production of reactive oxygen species (ROS), proinflammatory cytokines, and chemokines in maturing BMDCs that were activated by LPS. Therefore, DXM abrogated the ability of LPS-stimulated DCs to induce Ag-specific T-cell activation, as determined by their decreased proliferation and IFN-γ secretion in mixed leukocyte cultures. Moreover, the inhibition of LPS-induced MAPK activation and NF-B translocation may contribute to the suppressive effect of DXM on BMDCs. Remarkably, DXM decreased the LPS-induced surface expression of CD80, CD83, and HLA-DR and the secretion of IL-6 and IL-12 in human monocyte-derived dendritic cells (MDDCs). These findings provide a new insight into the impact of DXM treatment on DCs and suggest that DXM has the potential to be used in treating DC-related acute and chronic diseases. ? 2013 Der-Yuan Chen et al.
SDGs
Other Subjects
B7 antigen; CD83 antigen; dextromethorphan; gamma interferon; HLA DR antigen; immunoglobulin enhancer binding protein; lipopolysaccharide; reactive oxygen metabolite; antitussive agent; dextromethorphan; gamma interferon; HLA DR antigen; immunoglobulin enhancer binding protein; interleukin 12; interleukin 6; leukocyte antigen; lipopolysaccharide; mitogen activated protein kinase; reactive oxygen metabolite; antitussive agent; animal cell; animal experiment; article; cell activation; cell function; cell proliferation; controlled study; cytokine release; dendritic cell; drug effect; female; mixed leukocyte culture; mouse; nonhuman; priority journal; T lymphocyte activation; animal; C57BL mouse; cell culture; cytology; dendritic cell; drug effects; gene expression; genetics; human; immunology; lymphocyte activation; metabolism; signal transduction; T lymphocyte; lymphocyte activation; Animals; Antigens, CD; Antitussive Agents; Cells, Cultured; Dendritic Cells; Dextromethorphan; Female; Gene Expression; HLA-DR Antigens; Humans; Interferon-gamma; Interleukin-12; Interleukin-6; Lipopolysaccharides; Lymphocyte Activation; Mice; Mice, Inbred C57BL; Mitogen-Activated Protein Kinases; NF-kappa B; Reactive Oxygen Species; Signal Transduction; T-Lymphocytes; Animals; Antigens, CD; Antitussive Agents; Cells, Cultured; Dendritic Cells; Dextromethorphan; Female; Gene Expression; HLA-DR Antigens; Humans; Interferon-gamma; Interleukin-12; Interleukin-6; Lipopolysaccharides; Lymphocyte Activation; Mice; Mice, Inbred C57BL; Mitogen-Activated Protein Kinases; NF-kappa B; Reactive Oxygen Species; Signal Transduction; T-Lymphocytes
Type
journal article