Irinotecan (CPT-11)-induced elevation of bile acids potentiates suppression of IL-10 expression

doi:10.1016/j.laap.2015.12.003

	Irinotecan (CPT-11)-induced elevation of bile acids potentiates suppression of IL-10 expression
	Fang, Zhong-Ze 1,2,3,4; Zhang, Dunfang 5; Cao, Yun-Feng 3,4; Xie, Cen 1; Lu, Dan 6; Sun, Dong-Xue 1; Tanaka, Naoki 1; Jiang, Changtao 1; Chen, Qianming 5; Chen, Yu 5
刊名	TOXICOLOGY AND APPLIED PHARMACOLOGY
	2016-01-15
卷号	291 页码:21-27
关键词	Irinotecan (Cpt-11) Metabolomics Bile Acids Interleukin-10
ISSN号	0041-008X
DOI	10.1016/j.laap.2015.12.003
文献子类	Article
英文摘要	Irinotecan (CPT-11) is a first-line anti-colon cancer drug, however; CPT-11-induced toxicity remains a key factor limiting its clinical application. To search for clues to the mechanism of CPT-11-induced toxicity, metabolomics was applied using ultra-performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight mass spectrometry. Intraperitoneal injection of 50 mg/kg of CPT-11 induced loss of body weight, and intestine toxicity. Changes in gallbladder morphology suggested alterations in bile acid metabolism, as revealed at the molecular level by analysis of the liver, bile, and ileum metabolomes between the vehicle treated control group and the CPT-11-treated group. Analysis of immune cell populations further showed that CPT-11 treatment significantly decreased the IL-10-producing CD4 T cell frequency in intestinal lamina propria lymphocytes, but not in spleen or mesenteric lymph nodes. In vitro cell culture studies showed that the addition of bile acids deoxycholic acid and taurodeoxycholic acid accelerated the CPT-11-induced suppression of IL-10 secretion by activated CD4(+) naive T cells isolated from mouse splenocytes. These results showed that CPT-11 treatment caused metabolic changes in the composition of bile acids that altered CPT-11-induced suppression of IL-10 expression. Published by Elsevier Inc.
WOS关键词	INTESTINAL MUCOSITIS ; INDUCED COLITIS ; MICE ; CHEMOTHERAPY ; GLUCURONIDATION ; HEPATOTOXICITY ; INHIBITION ; METABOLISM ; TOXICITY ; PROTECTS
WOS研究方向	Pharmacology & Pharmacy ; Toxicology
语种	英语
出版者	ACADEMIC PRESS INC ELSEVIER SCIENCE
WOS记录号	WOS:000378100100003
内容类型	期刊论文
源URL	[http://cas-ir.dicp.ac.cn/handle/321008/170524]
专题	大连化学物理研究所_中国科学院大连化学物理研究所
通讯作者	Gonzalez, Frank J.
作者单位	1.NCI, Lab Metab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA 2.Tianjin Med Univ, Sch Publ Hlth, Dept Toxicol, Tianjin, Peoples R China 3.Chinese Acad Sci, Dalian Inst Chem Phys, Joint Ctr Translat Med, Dalian, Peoples R China 4.Liaoning Med Univ, Affiliated Hosp 1, Dalian, Peoples R China 5.Sichuan Univ, State Key Lab Oral Dis, West China Hosp Stomatol, Chengdu 610064, Peoples R China 6.Tianjin Med Univ, Dept Immunol, Tianjin Key Lab Cellular & Mol Immunol, Tianjin, Peoples R China 7.Shandong Univ, Sch Pharmaceut Sci, Jinan 250100, Peoples R China
推荐引用方式 GB/T 7714	Fang, Zhong-Ze,Zhang, Dunfang,Cao, Yun-Feng,et al. Irinotecan (CPT-11)-induced elevation of bile acids potentiates suppression of IL-10 expression[J]. TOXICOLOGY AND APPLIED PHARMACOLOGY,2016,291:21-27.
APA	Fang, Zhong-Ze.,Zhang, Dunfang.,Cao, Yun-Feng.,Xie, Cen.,Lu, Dan.,...&Gonzalez, Frank J..(2016).Irinotecan (CPT-11)-induced elevation of bile acids potentiates suppression of IL-10 expression.TOXICOLOGY AND APPLIED PHARMACOLOGY,291,21-27.
MLA	Fang, Zhong-Ze,et al."Irinotecan (CPT-11)-induced elevation of bile acids potentiates suppression of IL-10 expression".TOXICOLOGY AND APPLIED PHARMACOLOGY 291(2016):21-27.