IL-6 rescues enterocytes from hemorrhage induced apoptosis in vivo and in vitro by a bcl-2 mediated mechanism
IL-6 rescues enterocytes from hemorrhage induced apoptosis in vivo and in vitro by a bcl-2 mediated mechanism
复制标题
DOI：
10.1006/clin.1998.4600
复制
发表时间：
1998-12-01
期刊：
影响因子：
--
通讯作者：
Pacheco, ND
中科院分区：
文献类型：
--
作者：
Rollwagen, FM;Yu, ZY;Pacheco, ND
在发生出血事件后，对高代谢的肠道组织的破坏会导致屏障功能的丧失，导致细菌逃逸和宿主的内毒素污染。在大鼠和小鼠模型中，口服IL-6可以恢复出血后的肠道屏障功能，IL-6通过激活原癌基因bcl2来阻止各种淋巴样细胞和细胞系的凋亡。这种交流阐明了IL-6-bcl2相互作用在失血性休克后肠道细胞凋亡中的作用。采用末端脱氧核苷酸转移酶介导的dUTP缺口末端标记法(TUNEL)和p53免疫组织化学染色方法，观察给予生理盐水、IL-6和肠上皮细胞(IEC-6)低氧+内毒素或内毒素+IL-6的小鼠肠道组织。用BT原位杂交法检测失血小鼠肠道或肠上皮细胞bcl2的表达，结果表明，与失血小鼠灌服生理盐水的肠切片相比，失血小鼠肠组织切片的细胞凋亡率减少，bcl2基因表达增加。低氧和内毒素联合作用下的IEC-6细胞可见大量的TUNEL染色细胞。在低氧和内毒素处理后再暴露于IL-6可减少凋亡细胞数，增加bcl2基因的表达，数据表明，无论是口服IL-6还是低氧和内毒素处理后的共培养，肠上皮细胞暴露于IL-6都能增加bcl2基因的表达，减少细胞凋亡造成的损伤。(C)1998年学术出版社。
Following a hemorrhagic event, damage to the highly metabolic intestinal tissue induces loss of barrier function leading to bacterial escape and LPS contamination of the host. Orally administered IL-6 restores intestinal barrier function following hemorrhage in both rat and mouse models, IL-6 prevents apoptosis in a variety of lymphoid cells and lines, through the activation of the proto-oncogene bcl-2. This communication elucidates the role of the IL-6-bcl-2 interaction in intestinal apoptosis following hemorrhagic shock. Terminal deoxynucleotidyl-transferase-mediated dUTP nick end labeling (TUNEL) and p53 immunohistochemical staining were used to examine intestines from mice hemorrhaged and fed saline or IL-6 and enterocytes (IEC-6) exposed to hypoxia and LPS alone or LPS and IL-6 in vitro. bt situ hybridization for bcl-2 expression was performed on intestines or enterocytes, Intestinal sections from mice hemorrhaged and fed IL-6 showed reduction in apoptosis and increases in bcl-2 gene expression relative to sections taken from mice hemorrhaged and fed saline. IEC-6 cells exposed to hypoxia and LPS had high numbers of TUNEL staining cells. Subsequent exposure to IL-6 after hypoxia and LPS reduced apoptotic cell numbers and increased bcl-2 gene expression, The data show that exposure of intestinal epithelial cells to IL-6 either by oral administration in hemorrhaged mice or by coculture following hypoxia and LPS treatment results in increased bcl-2 gene expression and reduced damage from apoptosis. (C) 1998 Academic Press.