Matrine derivate MASM suppresses LPS-induced phenotypic and functional maturation of murine bone marrow-derived dendritic cells

Int Immunopharmacol. 2016 Jul:36:59-66. doi: 10.1016/j.intimp.2016.04.022. Epub 2016 Apr 22.

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.

Keywords: Akt; Dendritic cells; MAPK; Matrine; Maturation; NF-κB.

MeSH terms

  • Alkaloids / pharmacology*
  • Animals
  • Anti-Inflammatory Agents / pharmacology*
  • Cell Differentiation / drug effects
  • Dendritic Cells / drug effects*
  • Dendritic Cells / physiology
  • Endocytosis / drug effects
  • Interleukin-12 / metabolism
  • Interleukin-6 / metabolism
  • Lipopolysaccharides / immunology
  • Lymphocyte Activation / drug effects
  • Matrines
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mitogen-Activated Protein Kinases / metabolism
  • NF-kappa B / metabolism
  • Phosphatidylinositol 3-Kinases / metabolism
  • Quinolizines / pharmacology*
  • Signal Transduction / drug effects
  • Sophora / immunology*
  • Th1 Cells / drug effects*
  • Th1 Cells / immunology
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Alkaloids
  • Anti-Inflammatory Agents
  • Interleukin-6
  • Lipopolysaccharides
  • NF-kappa B
  • Quinolizines
  • Tumor Necrosis Factor-alpha
  • Interleukin-12
  • Phosphatidylinositol 3-Kinases
  • Mitogen-Activated Protein Kinases
  • Matrines