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Shikonin inhibits maturation of bone marrow‐derived dendritic cells and suppresses allergic airway inflammation in a murine model of asthma
Author(s) -
Lee ChenChen,
Wang ChienNeng,
Lai YuTing,
Kang JawJou,
Liao JiunnWang,
Chiang BorLuen,
Chen HuiChen,
Cheng YuWen
Publication year - 2010
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.2010.00972.x
Subject(s) - immunology , ovalbumin , medicine , thymic stromal lymphopoietin , cd80 , allergic inflammation , cytokine , dendritic cell , bone marrow , eotaxin , inflammation , immune system , cd40 , cytotoxic t cell , biology , chemokine , in vitro , biochemistry
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.