Shikonin inhibits myeloid differentiation protein 2 to prevent LPS-induced acute lung injury

doi:10.1111/bph.14129

科研成果详情

题名	Shikonin inhibits myeloid differentiation protein 2 to prevent LPS-induced acute lung injury
作者	Zhang, Yali1,2; Xu, Tingting 3; Pan, Zheer4; Ge, Xiangting 3; Sun, Chuchu 1; Lu, Chun 3; Chen, Hongjin 1; Xiao, Zhongxiang2; Zhang, Bing 2; Dai, Yuanrong3; Liang, Guang1,2
发表日期	2018-03
发表期刊	BRITISH JOURNAL OF PHARMACOLOGY 影响因子和分区
语种	英语
原始文献类型	Article
其他关键词	RESPIRATORY-DISTRESS-SYNDROME ; TOLL-LIKE RECEPTOR ; NF-KAPPA-B ; INDUCED INFLAMMATORY RESPONSE ; INNATE IMMUNE-SYSTEM ; SIGNALING PATHWAY ; CONCISE GUIDE ; MURINE MODEL ; TNF-ALPHA ; LIPOPOLYSACCHARIDE
摘要	BACKGROUND AND PURPOSE Acute lung injury (ALI) is a challenging clinical syndrome, which manifests as an acute inflammatory response. Myeloid differentiation protein 2 (MD2) has an important role in mediating LPS-induced inflammation. Currently, there are no effective molecular-based therapies for ALI or viable biomarkers for predicting the severity of disease. Recent preclinical studies have shown that shikonin, a natural naphthoquinone, prevents LPS-induced inflammation. However, little is known about the underlying mechanisms. EXPERIMENTAL APPROACH The binding affinity of shikonin to MD2 was analysed using computer docking, surface plasmon resonance analysis and elisa. In vitro, the anti-inflammatory effect and mechanism of shikonin were investigated through elisa, real-time quantitative reverse transcription PCR, Western blotting and immunoprecipitation assay. In vivo, lung injury was induced by intratracheal administration of LPS and assessed by changes in the histopathological and inflammatory markers. The underlying mechanisms were investigated by immunoprecipitation in lung tissue. KEY RESULTS Shikonin directly bound to MD2 and interfered with the activation of toll-like receptor 4 (TLR4) induced by LPS. In cultured macrophages, shikonin inhibited TLR4 signalling and pro-inflammatory cytokine production. These effects were produced through suppression of key signalling proteins including the NF-kappa B and the MAPK pathway. We also showed that shikonin inhibits MD2-TLR4 complex formation and reduces LPS-induced inflammatory responses in a mouse model of ALI. CONCLUSIONS AND IMPLICATIONS Our studies have uncovered the mechanism underlying the biological activity of shikonin in ALI and suggest that the targeting of MD2 may prove to be beneficial as a treatment option for this condition.
资助项目	Natural Science Funding of China [81622043, 81503123, 81570027]; Zhejiang Provincial Natural Science Funding [LY18H310011, LR16H310001, LY13H060007, LY16H010007]; Public Welfare Science and Technology Project of Wenzhou [Y20170087]
出版者	WILEY
出版地	HOBOKEN
ISSN	0007-1188
EISSN	1476-5381
卷号	175 期号:5 页码:840-854
DOI	10.1111/bph.14129
页数	15
WOS类目	Pharmacology & Pharmacy
WOS研究方向	Pharmacology & Pharmacy
WOS记录号	WOS:000425011300007
收录类别	SCIE ; SCOPUS ; PUBMED
URL	查看原文
PubMed ID	29243243
SCOPUSEID	2-s2.0-85041062746
自科自定义期刊分类	T3(B)类
通讯作者地址	[Zhang, Bing]Affiliated Yueqing Hospital,Wenzhou Medical University,Wenzhou,China
Scopus学科分类	Pharmacology
引用统计	被引频次：43[WOS] [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/14518
专题	药学院（分析测试中心）附属第二医院附属第一医院第二临床医学院、附属第二医院、育英儿童医院第一临床医学院（信息与工程学院）、附属第一医院_外科学_整形外科其他_附属乐清医院（乐清市人民医院）
通讯作者	Zhang, Bing
作者单位	1.Chemical Biology Research Center,School of Pharmaceutical Sciences,Wenzhou Medical University,Wenzhou,China; 2.Affiliated Yueqing Hospital,Wenzhou Medical University,Wenzhou,China; 3.The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University,Wenzhou,China; 4.Department of Orthopedic Surgery,The First Affiliated Hospital,Wenzhou Medical University,Wenzhou,China
第一作者单位	药学院（分析测试中心）; 生物有机与药物化学研究中心; 附属乐清医院（乐清市人民医院）
通讯作者单位	附属乐清医院（乐清市人民医院）
第一作者的第一单位	药学院（分析测试中心）
推荐引用方式 GB/T 7714	Zhang, Yali,Xu, Tingting,Pan, Zheer,et al. Shikonin inhibits myeloid differentiation protein 2 to prevent LPS-induced acute lung injury[J]. BRITISH JOURNAL OF PHARMACOLOGY,2018,175(5):840-854.
APA	Zhang, Yali., Xu, Tingting., Pan, Zheer., Ge, Xiangting., Sun, Chuchu., ... & Liang, Guang. (2018). Shikonin inhibits myeloid differentiation protein 2 to prevent LPS-induced acute lung injury. BRITISH JOURNAL OF PHARMACOLOGY, 175(5), 840-854.
MLA	Zhang, Yali,et al."Shikonin inhibits myeloid differentiation protein 2 to prevent LPS-induced acute lung injury".BRITISH JOURNAL OF PHARMACOLOGY 175.5(2018):840-854.