Isorhamnetin, the active constituent of a Chinese herb Hippophae rhamnoides L, is a potent suppressor of dendritic-cell maturation and trafficking

Int Immunopharmacol. 2018 Feb:55:216-222. doi: 10.1016/j.intimp.2017.12.014. Epub 2017 Dec 22.

Abstract

Dendritic cells (DCs) have been recognized as major targets of immunosuppressive therapies for their significant roles in connecting innate and adaptive immunity. Isorhamnetin (Iso), one of the most common flavonoid compounds extracted from the Chinese herb Hippophae rhamnoides L, has been proved to have anti-inflammatory, anticarcinogenic, and antioxidant activities in many chronic inflammatory conditions, but the effects of Iso on DCs have rarely been reported before. Here we investigated the functions and the mechanisms of Iso on bone marrow-derived DCs (BMDCs) including maturation, phagocytosis, and trafficking. Our data showed that Iso effectively inhibited the maturation of lipopolysaccharide (LPS)-treated BMDCs by down regulation of tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-1β and IL-12p70, up regulation of IL-10, and depression of costimulatory molecules CD40, CD80, and CD86, while had no effects on phagocytosis. Furthermore, Iso inhibited the migration of LPS-treated BMDCs, which may be due to its inhibition on chemokine receptor 7 (CCR7) expression. These findings strongly suggest that Iso is a potent immunosuppressive agent by inhibiting DC activation and trafficking, and may be used to prevent or treat chronic inflammation, autoimmune diseases, and graft rejections.

Keywords: Dendritic cells; Isorhamnetin; Maturation; Trafficking.

MeSH terms

  • Animals
  • Bone Marrow Cells / physiology
  • CD40 Antigens / metabolism
  • Cell Differentiation
  • Cell Movement
  • Cells, Cultured
  • Cytokines / metabolism
  • Dendritic Cells / physiology*
  • Hippophae / immunology
  • Immunologic Factors / therapeutic use*
  • Immunosuppression Therapy
  • Inflammation Mediators / metabolism
  • Lipopolysaccharides / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Phagocytosis
  • Quercetin / analogs & derivatives*
  • Quercetin / therapeutic use

Substances

  • CD40 Antigens
  • Cytokines
  • Immunologic Factors
  • Inflammation Mediators
  • Lipopolysaccharides
  • 3-methylquercetin
  • Quercetin