Suppressive effect of β, β-dimethylacryloyl alkannin on activated dendritic cells in an imiquimod-induced psoriasis mouse model

Int J Clin Exp Pathol. 2015 Jun 1;8(6):6665-73. eCollection 2015.

Abstract

Purpose: To investigate the effect of β, β-dimethylacryloyl alkannin, a main component of Lithospermum erythrorhizon, on activated dendritic cells (DCs) in a psoriasis mouse model.

Methods: BALB/c mice were used to establish the animal model for psoriasis-like skin lesion; alkannin at 10 mg/kg (high), 5 mg/kg (medium), 2.5 mg/kg (low), respectively, were intragastrically administered. Psoriasis area and severity index (PASI) was used to evaluate the skin lesions. Histological changes, the thickness of epidermis, and the quantity of interleukin (IL)-23 in skin lesion were measured. In in vitro experiments, mononuclear cells in peripheral blood from healthy people were isolated, and monocytes were obtained. DCs with a mature state in differentiation and function were obtained through in vitro induction with several cytokines, and identified by flow cytometry. The influence of DCs on proliferation of allogenic lymphocytes was analyzed. The influence of alkannin on messenger ribonucleic acid (mRNA) expression of pro-inflammatory factors by mature DCs was evaluated using reverse transcriptase polymerase chain reaction.

Results: Mice treated with alkannin at varying concentration showed obvious remission in psoriasis-like skin lesion compared to control group, with decreased PASI score, obviously reduced vertical thickness of epidermis. Besides, alkannin treatment decreased the expression of IL-23 in skin lesion. Alkannin (12.5 μg/mL) suppressed the ability of DCs to stimulate the proliferation of allogenic lymphocytes, and suppressed the expression and secretion of IL-6, IL-12 p40, IL-23, IL-1β, tumor necrosis factor-α mRNA and proteins, respectively.

Conclusions: β, β-dimethylacryloyl alkannin could suppress the function of activated DCs in imiquimod-induced psoriasis mouse model.

Keywords: L-shikonin; Lithospermum erythrorhizon; dendritic cells; psoriasis; β; β-dimethylacryloyl alkannin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aminoquinolines*
  • Animals
  • Cell Proliferation / drug effects
  • Cells, Cultured
  • Coculture Techniques
  • Cytokines / genetics
  • Cytokines / metabolism
  • Dendritic Cells / drug effects*
  • Dendritic Cells / immunology
  • Dendritic Cells / metabolism
  • Dermatologic Agents / pharmacology*
  • Disease Models, Animal
  • Humans
  • Imiquimod
  • Inflammation Mediators / metabolism
  • Lymphocyte Activation / drug effects
  • Lymphocytes / drug effects
  • Lymphocytes / immunology
  • Male
  • Mice, Inbred BALB C
  • Naphthoquinones / pharmacology*
  • Psoriasis / chemically induced
  • Psoriasis / drug therapy*
  • Psoriasis / genetics
  • Psoriasis / immunology
  • Psoriasis / metabolism
  • Psoriasis / pathology
  • Severity of Illness Index
  • Skin / drug effects*
  • Skin / immunology
  • Skin / metabolism
  • Skin / pathology
  • Time Factors

Substances

  • Aminoquinolines
  • Cytokines
  • Dermatologic Agents
  • Inflammation Mediators
  • Naphthoquinones
  • beta,beta-dimethylacryloyl alkannin
  • alkannin
  • Imiquimod