期刊
BRITISH JOURNAL OF PHARMACOLOGY
卷 161, 期 7, 页码 1496-1511出版社
WILEY-BLACKWELL PUBLISHING, INC
DOI: 10.1111/j.1476-5381.2010.00972.x
关键词
shikonin; dendritic cells; asthma; allergic inflammation; airway hyperresponsiveness
资金
- National Science Council in Taiwan [NSC 97-2320-B-039-007-MY3]
- China Medical University [CMU 96-252, 97-283]
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 mg.mL(-1)) and thymic stromal lymphopoietin (TSLP; 20 ng.mL(-1)). Shikonin-treated BM-DCs were poor stimulators of CD(4+) T lymphocyte and induced lower levels of interleukin (IL)-4, IL-5, IL-13 and tumour necrosis factor (TNF)-alpha 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-alpha 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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