Matrine derivate MASM suppresses LPS-induced phenotypic and functional maturation of murine bone marrow-derived dendritic cells.
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.
Department of Pharmacy, Shanghai East Hospital, Tongji University, Shanghai 310000, China; College of Pharmacy, Second Military Medical University, Shanghai 200433, China.
Jing
J
Xu
College of Pharmacy, Second Military Medical University, Shanghai 200433, China.
Yang
Y
Qi
College of Pharmacy, Second Military Medical University, Shanghai 200433, China.
Wei-Heng
WH
Xu
Department of Pharmacy, Shanghai East Hospital, Tongji University, Shanghai 310000, China.
Ying
Y
Liu
College of Pharmacy, Second Military Medical University, Shanghai 200433, China.
Lie
L
Qiu
College of Pharmacy, Second Military Medical University, Shanghai 200433, China.
Ke-Qi
KQ
Wang
College of Pharmacy, Second Military Medical University, Shanghai 200433, China.
Hong-Gang
HG
Hu
Department of Pharmacy, Shanghai East Hospital, Tongji University, Shanghai 310000, China.
Zhi-Gao
ZG
He
College of Pharmacy, Second Military Medical University, Shanghai 200433, China. Electronic address: jpzhang08@163.com.
Jun-Ping
JP
Zhang
D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects; D003713:Dendritic Cells / Q000187:drug effects* / Q000502:physiology; D004705:Endocytosis / Q000187:drug effects; D018664:Interleukin-12 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D011807:Quinolizines / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D029909:Sophora / Q000276:immunology*; D018417:Th1 Cells / Q000187:drug effects* / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D000093842:Matrines
D000470:Alkaloids; D000893:Anti-Inflammatory Agents; D015850:Interleukin-6; D008070:Lipopolysaccharides; D016328:NF-kappa B; D011807:Quinolizines; D014409:Tumor Necrosis Factor-alpha; D018664:Interleukin-12; D019869:Phosphatidylinositol 3-Kinases; D020928:Mitogen-Activated Protein Kinases; D000093842:Matrines
Akt; Dendritic cells; MAPK; Matrine; Maturation; NF-κB