May 28, 2013

Dextromethorphan Inhibits Activations and Functions in Dendritic Cells

Clinical and Developmental Immunology
Volume 2013 (2013), Article ID 125643, 11 pages
http://dx.doi.org/10.1155/2013/125643
Research Article

Dextromethorphan Inhibits Activations and Functions in Dendritic Cells

1Institute of Biomedical Science, National Chung-Hsing University, Taichung 402, Taiwan
2Faculty of Medicine, National Yang-Ming University, Taipei 112, Taiwan
3Division of Allergy, Immunology and Rheumatology, Taichung Veterans General Hospital, Taichung 407, Taiwan
4Laboratory of Toxicology and Pharmacology, National Institutes of Environmental, Health Sciences, Research Triangle Park, NC 27709, USA
5Graduate Institute of Immunology, College of Medicine, National Taiwan University, Taipei 100, Taiwan
6Biomedical Technology and Device Research Laboratories, Industrial Technology Research Institute, Hsinchu 300, Taiwan
7Institute of Clinical Medicine, National Yang-Ming University, Taipei 112, Taiwan
8Division of Chest Medicine, Department of Internal Medicine, Changhua Christian Hospital, Changhua 500, Taiwan
9Department of Respiratory Care, College of Health Sciences, Chang Jung Christian University, Tainan 711, Taiwan
10School of Medicine, Chung Shan Medical University, Taichung 402, Taiwan
11Department of Medical Research and Education, Taichung Veterans General Hospital, Taichung 407, Taiwan
Received 1 February 2013; Accepted 25 March 2013
Academic Editor: Beatrice Gaugler
Copyright © 2013 Der-Yuan Chen et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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-κB 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.

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