Induction by activated macrophage-like THP-1 cells of apoptotic and necrotic cell death in intestinal epithelial Caco-2 monolayers via tumor necrosis factor-alpha.
Induction by activated macrophage-like THP-1 cells of apoptotic and necrotic cell death in intestinal epithelial Caco-2 monolayers via tumor necrosis factor-alpha.
复制标题
DOI：
10.1016/j.yexcr.2006.08.018
复制
发表时间：
2006-11
影响因子：
3.7
通讯作者：
H. Satsu;Yoko Ishimoto;T. Nakano;T. Mochizuki;T. Iwanaga;M. Shimizu
中科院分区：
文献类型：
--
作者：
H. Satsu;Yoko Ishimoto;T. Nakano;T. Mochizuki;T. Iwanaga;M. Shimizu
肠上皮细胞通过可溶性因子与位于肠上皮中的免疫细胞相互作用。本研究以人肠上皮样细胞Caco-2单层和活化的巨噬细胞样细胞THP-1细胞为研究对象，建立了一个共培养的体外模型系统，以分析巨噬细胞对肠上皮细胞的影响。与THP-1细胞共培养导致Caco-2乳酸脱氢酶释放增加，单层跨上皮电阻降低，表明与THP-1共培养诱导Caco-2细胞损伤。加入抗TNF-α抗体和依那西普可显著抑制这种破坏，这强烈表明THP-1分泌的TNF-α对Caco-2单层造成了细胞损伤。破坏的Caco-2单层细胞的形态学和生化分析显示凋亡和坏死的特点。TNFRI和NF-κB B可能参与了这一调节过程。这表明，这种现象在某些方面与IBD观察到的相似，并且这种体外共培养系统可能是寻找可用于治疗或预防IBD的药物或食品的良好模型。
Intestinal epithelial cells interact with immune cells located in the intestinal epithelium via soluble factors. An in vitro model system using coculture was constructed to analyze the effect of macrophages on intestinal epithelial cells, and human intestinal epithelial-like Caco-2 monolayers and activated macrophage-like THP-1 cells were used in this study. Coculturing with THP-1 cells resulted in an increase of lactate dehydrogenase release from Caco-2 and a decrease in the transepithelial electrical resistance of the monolayers, showing that coculturing with THP-1 induced cell damage to Caco-2 cells. This disruption was significantly suppressed by adding anti-TNF-α antibody and etanercept, strongly suggesting that TNF-α secreted from THP-1 had caused cell damage to Caco-2 monolayers. The disrupted Caco-2 monolayers showed both apoptotic and necrotic characteristics by morphological and biochemical analyses. TNFRI and NF-κB seem to have been involved in this regulation. It is suggested that this phenomenon is similar in some respects to that observed with IBD and that this in vitro coculture system could be a good model for searching for the drugs or food substances that can be used to treat or prevent IBD.