机构：[a]Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA[b]Department of Toxicology, School of Public Health, Tianjin Medical University, Tianjin, China[c]Joint Center for Translational Medicine, Dalian Institute of Chemical Physics, Chinese Academy of Sciences and First Affiliated Hospital of Liaoning Medical University, Dalian, China大连医科大学附属第一医院[d]State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China[e]Department of Immunology, Tianjin Key Laboratory of Cellular and Molecular Immunology, Tianjin Medical University, Tianjin, China[f]School of Pharmaceutical Sciences, Shandong University, Jinan, China
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.
基金：
This study was funded by the Intramural Research Program of the
Center for Cancer Research, National Cancer Institute, National Natural
Science Foundation of China (No. 81202586), Tianjin Project of
Thousand Youth Talents, and Natural Science Foundation of Shandong
Province (Nos. BS2013YY054 and ZR2010HL023).
语种：
外文
PubmedID：
中科院(CAS)分区：
出版当年[2016]版：
大类|2 区医学
小类|2 区药学2 区毒理学
最新[2023]版：
大类|3 区医学
小类|2 区毒理学3 区药学
第一作者：
第一作者机构：[a]Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA[b]Department of Toxicology, School of Public Health, Tianjin Medical University, Tianjin, China[c]Joint Center for Translational Medicine, Dalian Institute of Chemical Physics, Chinese Academy of Sciences and First Affiliated Hospital of Liaoning Medical University, Dalian, China
通讯作者：
通讯机构：[a]Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA[*1]Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
推荐引用方式(GB/T 7714)：
Zhong-Ze Fang,Dunfang Zhang,Yun-Feng Cao,et al.Irinotecan (CPT-11)-induced elevation of bile acids potentiates suppression of IL-10 expression.[J].Toxicology and applied pharmacology.2016,291:21-7.doi:10.1016/j.taap.2015.12.003.
APA：
Zhong-Ze Fang,Dunfang Zhang,Yun-Feng Cao,Cen Xie,Dan Lu...&Frank J. Gonzalez.(2016).Irinotecan (CPT-11)-induced elevation of bile acids potentiates suppression of IL-10 expression..Toxicology and applied pharmacology,291,
MLA：
Zhong-Ze Fang,et al."Irinotecan (CPT-11)-induced elevation of bile acids potentiates suppression of IL-10 expression.".Toxicology and applied pharmacology 291.(2016):21-7
