Dextromethorphan Inhibits Activations and Functions in Dendritic Cells

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.

Vibrio cholerae ghosts (VCG) exert immunomodulatory effect on dendritic cells for enhanced antigen presentation and induction of protective immunity

“…The interaction of VCGs with BMDC stimulated the expression of co-stimulatory molecules associated with DC activation and maturation. In addition, there is enhanced expression of major histocompatibility complex molecules (MHC) and these surface molecules mediate adhesion with T cells during antigen presentation [ 27 ]. Consistent with previous findings [ 28 ], stimulation of BMDCs with UV-EBs for 24 h resulted in the significant up-regulation of costimulatory molecules (CD40, CD80, CD83 and CD86) and class II major histocompatibility complex molecules (MHC II) that was enhanced by co-culture with VCGs.…”

Bursopentin (BP5) Protects Dendritic Cells from Lipopolysaccharide-Induced Oxidative Stress for Immunosuppression

“…In the pathogenesis of type 1 diabetes, ROS not only cause direct damage to β cells, but also participate actively in inflammation [ 18 ]. Control of oxidative stress can be achieved through a variety of means, including dietary antioxidants, such as β-carotene [ 19 ], vitamin C [ 20 ], lycopene [ 21 ], and a combination of vitamins C and E [ 22 ], or through pharmaceutical intervention, using anti-inflammatory drugs such as dextromethorphan [ 23 ], panax quinquefolium saponins [ 24 ], and fisetin [ 25 ]. As many of these compounds have been shown to exert anti-inflammatory effects by inhibiting the activation and maturation of DCs, the use of these or other antioxidants may be useful for the management of inflammatory diseases associated with DC activity.…”

Identification of Primary Natural Killer Cell Modulators by Chemical Library Screening with a Luciferase-Based Functional Assay

“…Interestingly, several of these molecules fall into pharmacological classes of drugs previously identified by Theorell & al. 34 as modulators of antibody-dependent NK cytotoxicity, including adrenergic receptor ligands inhibiting the maturation of conventional dendritic cells 36 , but also disease progression in experimental mouse models of autoimmune disorders 37,38 , or inflammation and oxidative stress in heavy smokers 39 . Mechanisms involved are still poorly understood, but could also control the activation of NK cells.…”