TY - JOUR
T1 - Shikonin inhibits maturation of bone marrow-derived dendritic cells and suppresses allergic airway inflammation in a murine model of asthma
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
PY - 2010/12
Y1 - 2010/12
N2 - 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.
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.
KW - Airway hyperresponsiveness
KW - Allergic inflammation
KW - Asthma
KW - Dendritic cells
KW - Shikonin
KW - Airway hyperresponsiveness
KW - Allergic inflammation
KW - Asthma
KW - Dendritic cells
KW - Shikonin
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U2 - 10.1111/j.1476-5381.2010.00972.x
DO - 10.1111/j.1476-5381.2010.00972.x
M3 - Article
C2 - 20735407
AN - SCOPUS:78149395454
SN - 0007-1188
VL - 161
SP - 1496
EP - 1511
JO - British Journal of Pharmacology
JF - British Journal of Pharmacology
IS - 7
ER -