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


METHODS
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.


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.


CONCLUSIONS
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.
Lee
Chen-Chen
CC
Department of Microbiology and Immunology, School of Medicine, China Medical University, Taichung, Taiwan.
Wang
Chien-Neng
CN
Lai
Yu-Ting
YT
Kang
Jaw-Jou
JJ
Liao
Jiunn-Wang
JW
Chiang
Bor-Luen
BL
Chen
Hui-Chen
HC
Cheng
Yu-Wen
YW
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001249:Asthma / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D001854:Bone Marrow Cells / Q000187:drug effects* / Q000276:immunology; D001992:Bronchoalveolar Lavage Fluid; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology; D004365:Drugs, Chinese Herbal / Q000378:metabolism / Q000494:pharmacology; D005260:Female; D007249:Inflammation / Q000188:drug therapy / Q000276:immunology / Q000473:pathology; D018793:Interleukin-13 / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D015848:Interleukin-5 / Q000378:metabolism; D008168:Lung / Q000276:immunology / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D009285:Naphthoquinones / Q000494:pharmacology*; D010047:Ovalbumin / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D000094632:Thymic Stromal Lymphopoietin
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016207:Cytokines; D004365:Drugs, Chinese Herbal; D018793:Interleukin-13; D015848:Interleukin-5; D009285:Naphthoquinones; D014409:Tumor Necrosis Factor-alpha; D015847:Interleukin-4; C016101:shikonin; D010047:Ovalbumin; D000094632:Thymic Stromal Lymphopoietin; C000721967:TSLP protein, mouse