CDNA array analysis of cytokines, chemokines, and receptors involved in the development of TNBS-induced colitis:: Homeostatic role of VIP
CDNA array analysis of cytokines, chemokines, and receptors involved in the development of TNBS-induced colitis:: Homeostatic role of VIP
复制标题
DOI：
10.1097/01.mib.0000171872.70738.58
复制
发表时间：
2005-07-01
影响因子：
4.9
通讯作者：
Gomariz, RP
中科院分区：
文献类型：
--
作者：
Abad, C;Juarranz, Y;Gomariz, RP
克罗恩病（CD）是一种肠道慢性炎症性病变，以腹泻和体重减轻为特征。先前已显示血管活性肠肽（VIP）在基于2，4，6-三硝基苯磺酸（TNBS）给药的CD鼠模型中的愈合作用。这项工作的目的是分析结肠炎和VIP治疗的动物中与炎症级联反应相关的几种介质的表达。为此目的，小鼠隔日仅接受TNBS或TNBS和VIP治疗。对来自结肠的总mRNA进行cDNA微阵列分析和实时聚合酶链反应，以研究一系列促炎分子的表达，例如酶考克斯-2，趋化因子CX 3 CL 1、CXCL 12、CXCL 13、CXCL 14、CCR 5和CXCR 2，以及细胞因子白细胞介素（IL）-1 β、IL-12、IL-18、IL-10、干扰素-γ和IL-4。TNBS给药诱导了所有研究的促炎介质的表达，而VIP治疗降低了它们的水平，增加了抗炎IL-10和T（H）2细胞因子IL-4，解释了其通过抑制炎症/T（H）1反应的有益作用。这些数据不仅描述了几种促炎介质与TNBS结肠炎发展的关系，报告了它们的时间过程，而且还显示了VIP在该模型中通过完全阻断炎症级联反应和恢复结肠稳态的有益作用，为CID治疗提供了潜在的新替代方案。
Crohn's disease (CD) is a chronic inflammatory pathology of the intestine, characterized by diarrhea and weight loss. A healing effect of vasoactive intestinal peptide (VIP) in the murine model of CD based on 2,4,6-trinitrobencene sulfonic acid (TNBS) administration has been previously shown. The aim of this work was to analyze the expression of several mediators related to the inflammatory cascade in colitic and VIP-treated animals. With this aim, mice received either only TNBS or TNBS and VIP treatment on alternate days. cDNA microarray analysis and real-time polymerase chain reaction were performed on total mRNA from colon to study the expression of a battery of proinflammatory molecules such as the enzyme COX-2, the chemokines CX3CL1, CXCL12, CXCL13, CXCL14, CCR5, and CXCR2, and the cytokines interleukin (IL)-1 beta, IL-12, IL-18, IL-10, interferon-gamma, and IL-4. TNBS administration induced the expression of all the proinflammatory mediators studied, whereas VIP treatment reduced their levels, increasing the anti-inflammatory IL-10 and the T(H)2 cytokine IL-4, explaining its beneficial action through inhibition of the inflammatory/T(H)1 response. These data describe not only the relation of several proinflammatory mediators to the development of TNBS colitis, reporting their time-course, but also show the beneficial action of VIP in this model through complete blockage of the inflammatory cascade and recovery of the colon homeostasis, providing a potential new alternative for CID therapy.