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Adhesion molecules and liver inflammation after radiation: Role of PECAM-1.

粘附分子和辐射后肝脏炎症：PECAM-1 的作用。

基本信息

批准号：
225940717
负责人：
Dr. Ihtzaz Ahmed Malik
金额：
--
依托单位：
Klinik für Gastroenterologie und gastrointestinale Onkologie
依托单位国家：
德国
项目类别：
Research Grants
财政年份：
2012
资助国家：
德国
起止时间：
2011-12-31 至 2016-12-31
项目状态：
已结题

来源：
https://gepris.dfg.de/gepris/projekt/225940717?language=en
关键词：
Adhesion molecules liver inflammation after

项目摘要

The role of PECAM-1 (CD31) and CD99L2 in inflammation is still under debate. It is hypothesized that in inflammatory conditions, PECAM-1- (and possibly CD99L2)- down-regulation in parallel to ICAM-1-up-regulation is induced by TNF- through upregulation of NF-kB and downregulation of JNK allowing inflammatory cells to attach to and to transmigrate through the vessel wall (portal area). In contrast, TGF- could stop this process and/or help in repair. Effect of radiation on PECAM-1- and CD99L2- regulation will be studied after TNF- or TGF- administration in wild type mice and in PECAM-1-ko-mice. Immunohistology of liver sections, gene expression of cytokine- and target genes (PECAM-1, ICAM-1 and CD99L2) at mRNA and protein level will be performed. Furthermore, Laser capture microdissection (LCM) of liver sections will be used to measure amount of mRNA (PECAM-1, ICAM-1 and CD99L2) in the different areas of the liver lobule. Flow-cytometry analysis will be used to quantify PECAM-1, ICAM-1 and CD99L2 level on isolated liver and inflammatory cells. Gene expression will also be studied at RNA- (PCR, gene array) and protein level (Western blot) from sorted cell populations (by MACS-separator). Effect of TNF- and/or TGF- will be investigated in transmigration studies (granulocytes, macrophages) on cultured endothelial cells. The new knowledge will help to find therapeutic means to reduce radiation induced damage and fibrosis in the liver.

PECAM-1（CD 31）和CD 99 L2在炎症中的作用仍在争论中。假设在炎性条件下，与ICAM-1上调平行的PECAM-1（和可能的CD 99 L2）下调由TNF-α通过上调NF-kB和下调JNK诱导，从而允许炎性细胞附着并穿过血管壁（汇管区）。相反，TGF-β可以阻止这一过程和/或帮助修复。将在野生型小鼠和PECAM-1-ko-小鼠中研究TNF-或TGF-给药后辐射对PECAM-1-和CD 99 L2-调节的影响。将进行肝脏切片的免疫组织学检查，在mRNA和蛋白质水平进行细胞因子和靶基因（PECAM-1、ICAM-1和CD 99 L2）的基因表达。此外，肝脏切片的激光捕获显微切割（LCM）将用于测量肝小叶不同区域中mRNA（PECAM-1、ICAM-1和CD 99 L2）的量。流式细胞术分析将用于定量分离的肝脏和炎性细胞上的PECAM-1、ICAM-1和CD 99 L2水平。还将在RNA水平（PCR，基因阵列）和蛋白质水平（Western印迹）研究分选细胞群（通过MACS分离器）的基因表达。将在培养的内皮细胞的迁移研究（粒细胞、巨噬细胞）中研究TNF-和/或TGF-的影响。新的知识将有助于找到治疗方法，以减少辐射引起的肝脏损伤和纤维化。