3,3′-Diindolylmethane decreases VCAM-1 expression and alleviates experimental colitis via a BRCA1-dependent antioxidant pathway

被引:36
作者
Huang, Zhen [1 ]
Zuo, Longsheng [1 ]
Zhang, Zhengping [1 ]
Liu, Jialin [1 ]
Chen, Jiangning [1 ]
Dong, Lei [1 ]
Zhang, Junfeng [1 ,2 ,3 ]
机构
[1] Nanjing Univ, State Key Lab Pharmaceut Biotechnol, Sch Life Sci, Nanjing 210093, Peoples R China
[2] Nanjing Univ, Jiangsu Prov Diabet Ctr, Nanjing 210093, Peoples R China
[3] Nanjing Univ, Jiangsu Prov Lab Nanotechnol, Nanjing 210093, Peoples R China
基金
中国国家自然科学基金; 中国博士后科学基金;
关键词
3,3 '-Diindolylmethane; Inflammatory bowel disease; Reactive oxygen species; Vascular cell adhesion molecule 1; Free radicals; INFLAMMATORY-BOWEL-DISEASE; PROSTATE-CANCER CELLS; ENDOTHELIAL-CELLS; OXIDATIVE STRESS; FREE-RADICALS; AH RECEPTOR; ADHESION; BREAST; ICAM-1; MICE;
D O I
10.1016/j.freeradbiomed.2010.10.703
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Reactive oxygen species (ROS) exhibit a key role in the pathogenesis of inflammatory bowel disease (IBD). 3,3'-Diindolylmethane (DIM) can protect against oxidative stress in a breast cancer susceptibility gene 1 (BRCA1)-dependent manner. The aim of this study was to examine the therapeutic effects of DIM in experimental colitis and investigate the possible mechanisms underlying its effects on intestinal inflammation. The therapeutic effects of DIM were studied in 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis. Pathological markers of colitis severity, antioxidant activity, and ROS generation in colonic tissue were measured. The impact of DIM on ROS-induced endothelial vascular cell adhesion molecule 1 (VCAM-1) expression and leukocyte-endothelial cell interaction was further investigated in cultures of endothelial cells and in the TNBS-induced colitis model. Administration of DIM was demonstrated to attenuate experimental colitis, as judged by pathological indices. DIM could effectively stimulate the expression of BRCA1 in vitro and in vivo and reduce ROS generation, leading to the inhibition of VCAM-1 expression and leukocyte-endothelial cell adhesion, and finally resulted in an alleviation of experimental colitis. DIM has shown anti-IBD activity in animal models by inhibiting ROS-induced VCAM-1 expression and leukocyte recruitment via a BRCA1-dependent antioxidant pathway and thus may offer potential treatments for IBD patients. (C) 2010 Elsevier Inc. All rights reserved.
引用
收藏
页码:228 / 236
页数:9
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