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Matrine derivate MASM suppresses LPS-induced phenotypic and functional maturation of murine bone marrow-derived dendritic cells
Affiliation:1. Department of Pharmacy, Shanghai East Hospital, Tongji University, Shanghai 310000, China;2. College of Pharmacy, Second Military Medical University, Shanghai 200433, China;1. Department of Pathology, School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil;2. Pontifical Catholic University of Paraná, Londrina, PR, Brazil;3. Department of Pathological Sciences, State University of Londrina, Londrina, PR, Brazil
Abstract:Dendritic cell (DC) maturation process is a crucial step for the development of T cell immune responses and immune tolerance. In this study, we evaluated MASM, a novel derivative of the natural compound matrine that possesses a significant anti-inflammatory and immune-regulating property, for its efficacy to inhibit lipopolysaccharides (LPS)-induced maturation of murine bone marrow-derived dendritic cells. Here we show that MASM profoundly suppresses LPS-induced phenotypic and functional DC maturation. MASM inhibited LPS-induced expression of costimulatory molecules CD80 and CD86 in a concentration-dependent manner. MASM also attenuated LPS-induced IL-12p70, TNF-α, IL-6 and NO release of DCs. The MASM-treated DCs were highly efficient at antigen capture via mannose receptor-mediated endocytosis but showed weak stimulatory capacity for allogeneic T cell proliferation. Furthermore, MASM inhibited LPS-induced PI3K/Akt, MAPK and NF-κB pathways. These novel findings provide new insight into the immunopharmacological role of MASM in impacting on the DCs.
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