Shikonin inhibits maturation of bone marrow-derived dendritic cells and suppresses allergic airway inflammation in a murine model of asthma

Br J Pharmacol. 2010 Dec;161(7):1496-511. doi: 10.1111/j.1476-5381.2010.00972.x.

Abstract

Background and purpose: Shikonin exhibits a wide range of anti-inflammatory actions. Here, we assessed its effects on maturation of murine bone marrow-derived dendritic cells (BM-DCs) and on allergic reactions in a murine model of asthma.

Experimental approach: Cultured murine BM-DCs were used to investigate the effects of shikonin on expression of cell surface markers and their stimulation of T-cell proliferation and cytokine production. The therapeutic potential of shikonin was evaluated in a model of allergic airway disease.

Key results: Shikonin dose-dependently inhibited expression of major histocompatibility complex class II, CD80, CD86, CCR7 and OX40L on BM-DCs, induced by a mixture of ovalbumin (OVA; 100µg·mL(-1) ) and thymic stromal lymphopoietin (TSLP; 20ng·mL(-1) ). Shikonin-treated BM-DCs were poor stimulators of CD4(+) T lymphocyte and induced lower levels of interleukin (IL)-4, IL-5, IL-13 and tumour necrosis factor (TNF)-α release by responding T-cells. After intratracheal instillation of shikonin in OVA-immunized mice, OVA challenge induced lower IL-4, IL-5, IL-13, TNF-α and eotaxin release in bronchial alveolar lavage fluid, lower IL-4 and IL-5 production in lung cells and mediastinal lymph node cells and attenuated OVA-induced lung eosinophilia and airway hyperresponsiveness.

Conclusion and implications: Shikonin effectively suppressed OVA + TSLP-induced BM-DC maturation in vitro and inhibited allergic inflammation and airway hyperresponsiveness in a murine model of asthma, showing good potential as a treatment for allergic asthma. Also, our model provides a novel platform for screening drugs for allergic diseases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
  • Asthma / drug therapy*
  • Asthma / immunology
  • Asthma / pathology
  • Bone Marrow Cells / drug effects*
  • Bone Marrow Cells / immunology
  • Bronchoalveolar Lavage Fluid
  • Cytokines / metabolism
  • Dendritic Cells / drug effects*
  • Dendritic Cells / immunology
  • Drugs, Chinese Herbal / metabolism
  • Drugs, Chinese Herbal / pharmacology
  • Female
  • Inflammation / drug therapy
  • Inflammation / immunology
  • Inflammation / pathology
  • Interleukin-13 / metabolism
  • Interleukin-4 / metabolism
  • Interleukin-5 / metabolism
  • Lung / immunology
  • Lung / pathology
  • Mice
  • Mice, Inbred BALB C
  • Naphthoquinones / pharmacology*
  • Ovalbumin / immunology
  • Thymic Stromal Lymphopoietin
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Cytokines
  • Drugs, Chinese Herbal
  • Interleukin-13
  • Interleukin-5
  • Naphthoquinones
  • Tumor Necrosis Factor-alpha
  • Interleukin-4
  • shikonin
  • Ovalbumin
  • Thymic Stromal Lymphopoietin
  • TSLP protein, mouse