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

Chen Chen Lee, Chien Neng Wang, Yu Ting Lai, Jaw Jou Kang, Jiunn Wang Liao, Bor Luen Chiang, Hui Chen Chen, Yu Wen Cheng

Research output: Contribution to journalArticle

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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; 100 μg·mL -1) and thymic stromal lymphopoietin (TSLP; 20 ng·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.

Original languageEnglish
Pages (from-to)1496-1511
Number of pages16
JournalBritish Journal of Pharmacology
Volume161
Issue number7
DOIs
Publication statusPublished - Dec 2010

Fingerprint

Dendritic Cells
Asthma
Bone Marrow
Inflammation
Interleukin-5
Interleukin-4
Interleukin-13
T-Lymphocytes
Tumor Necrosis Factor-alpha
Lung
Preclinical Drug Evaluations
Ovalbumin
Bronchoalveolar Lavage Fluid
Eosinophilia
shikonin
Major Histocompatibility Complex
Hypersensitivity
Anti-Inflammatory Agents
Lymph Nodes
Cell Proliferation

Keywords

  • Airway hyperresponsiveness
  • Allergic inflammation
  • Asthma
  • Dendritic cells
  • Shikonin

ASJC Scopus subject areas

  • Pharmacology

Cite this

Shikonin inhibits maturation of bone marrow-derived dendritic cells and suppresses allergic airway inflammation in a murine model of asthma. / Lee, Chen Chen; Wang, Chien Neng; Lai, Yu Ting; Kang, Jaw Jou; Liao, Jiunn Wang; Chiang, Bor Luen; Chen, Hui Chen; Cheng, Yu Wen.

In: British Journal of Pharmacology, Vol. 161, No. 7, 12.2010, p. 1496-1511.

Research output: Contribution to journalArticle

Lee, Chen Chen ; Wang, Chien Neng ; Lai, Yu Ting ; Kang, Jaw Jou ; Liao, Jiunn Wang ; Chiang, Bor Luen ; Chen, Hui Chen ; Cheng, Yu Wen. / Shikonin inhibits maturation of bone marrow-derived dendritic cells and suppresses allergic airway inflammation in a murine model of asthma. In: British Journal of Pharmacology. 2010 ; Vol. 161, No. 7. pp. 1496-1511.
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AU - Lee, Chen Chen

AU - Wang, Chien Neng

AU - Lai, Yu Ting

AU - Kang, Jaw Jou

AU - Liao, Jiunn Wang

AU - Chiang, Bor Luen

AU - Chen, Hui Chen

AU - Cheng, Yu Wen

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AB - 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; 100 μg·mL -1) and thymic stromal lymphopoietin (TSLP; 20 ng·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.

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