Sinulariolide suppresses LPS-induced phenotypic and functional maturation of dendritic cells

Abstract

The dendritic cell (DC) maturation process is essential for the development of T cell responses and immune tolerance. Accordingly, DCs are considered a major target in the development of immunomodulating agents. In the present study, the effect of sinulariolide, an active compound isolated from the cultured soft coral Sinularia flexibilis, on lipopolysaccharide (LPS)-induced murine bone marrow-derived DCs was evaluated. The different phenotypes, cytokine secretion and the mix-lymphocyte reaction of DCs were detected using flow cytometry and ELISA. The experimental results revealed that the phenotypic and functional maturation of DCs stimulated by LPS were markedly reduced by sinulariolide in a concentration-dependent manner, including the expression of co-stimulatory molecules (CD40, CD80 and CD86). In addition, sinulariolide reduced the release of tumor necrosis factor-α, interleukin (IL)-6, IL-12 and nitric oxide from the LPS-activated DCs, decreased their abilities to stimulate allogeneic T cell proliferation, and inhibited LPS-induced nuclear factor-κB pathways. These findings offer novel insight into the immunopharmacological function of sinulariolide and its effects on DCs.