Radicicol, an Hsp90 inhibitor, inhibits intestinal inflammation and leakage in abdominal sepsis

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	Radicicol, an Hsp90 inhibitor, inhibits intestinal inflammation and leakage in abdominal sepsis
	Zhao, Yilin ; Huang, Zheng-Jie ; Rahman, Milladur ; Luo, Qi ; Thorlacius, Henrik ; Zhao YL(赵一麟) ; Huang ZJ(黄正接) ; Luo Q(罗琪)
刊名	http://dx.doi.org/10.1016/j.jss.2012.10.038
	2013
关键词	PROTEIN 90 INHIBITORS NECROSIS-FACTOR-ALPHA REGULATORY T-CELLS KINASE INHIBITOR BARRIER FUNCTION HEPATOCELLULAR APOPTOSIS LEUKOCYTE RECRUITMENT HEMORRHAGIC-SHOCK LIVER-INJURY LUNG INJURY
英文摘要	Swedish Medical Research Council [2009-4872]; Lund University; Allmana sjukhusets i Malmostiftelse for bekampande av cancer; MAS fonder; Malmo University Hospital; Background: Intestinal injury is a key feature in sepsis. Inhibitors of heat shock protein 90 (Hsp90) have been shown to exert protective effects in models of inflammation. Herein, we hypothesized that Hsp90 might regulate intestinal inflammation and leakage in abdominal sepsis. Materials and methods: Male C57BL/6 mice were pretreated with radicicol (60 mg/kg), which is a specific inhibitor of Hsp90, prior to cecal ligation and puncture (CLP). Intravital fluorescence microscopy was used to quantify leukocyte-endothelium interactions in the colonic microcirculation 6 h after CLP. Colonic tissue was harvested to determine levels of myeloperoxidase, tumor necrosis factor-alpha and CXC chemokines. Intestinal injury was examined by histology. Intestinal barrier function was quantified by leakage of fluorescein isothiocyanate-dextran from the vascular system out into the abdominal cavity after intravenous injection. Results: We found that radicicol significantly decreased CLP-induced leukocyte rolling and adhesion in colonic venules. Inhibition of Hsp90 reduced colonic levels of myeloperoxidase by 24% in septic animals. Moreover, radicicol significantly decreased CLP-provoked formation of CXC chemokines but had no significant effect on tumor necrosis factor-alpha levels in the colon. Notably, Hsp90 inhibition significantly attenuated intestinal tissue injury evoked by CLP. Lastly, it was found that radicicol reduced sepsis-induced intestinal leakage by 43%. Conclusion: Our novel findings suggest that targeting Hsp90 protects against intestinal inflammation and leakage and might be a useful strategy to ameliorate intestinal failure in polymicrobial sepsis. (C) 2013 Elsevier Inc. All rights reserved.
语种	英语
出版者	ACADEMIC PRESS INC ELSEVIER SCIENCE
内容类型	期刊论文
源URL	[http://dspace.xmu.edu.cn/handle/2288/93533]
专题	医学院－已发表论文
推荐引用方式 GB/T 7714	Zhao, Yilin,Huang, Zheng-Jie,Rahman, Milladur,et al. Radicicol, an Hsp90 inhibitor, inhibits intestinal inflammation and leakage in abdominal sepsis[J]. http://dx.doi.org/10.1016/j.jss.2012.10.038,2013.
APA	Zhao, Yilin.,Huang, Zheng-Jie.,Rahman, Milladur.,Luo, Qi.,Thorlacius, Henrik.,...&罗琪.(2013).Radicicol, an Hsp90 inhibitor, inhibits intestinal inflammation and leakage in abdominal sepsis.http://dx.doi.org/10.1016/j.jss.2012.10.038.
MLA	Zhao, Yilin,et al."Radicicol, an Hsp90 inhibitor, inhibits intestinal inflammation and leakage in abdominal sepsis".http://dx.doi.org/10.1016/j.jss.2012.10.038 (2013).