Bolcato-Bellemin Anne-Laure, Mattei Marie-Genevieve, Fenton Matthew, Amar Salomon
Center for the Advanced Biomedical Research, Boston University, Massachusetts 02118, USA.
J Endotoxin Res. 2004;10(1):15-23. doi: 10.1179/096805104225003780.
The inflammatory response to bacteria and bacterial products, such as lipopolysaccharides (LPSs), is mediated by a variety of secreted factors, but cytotoxic effects of LPS have been ascribed to the tumor necrosis factor alpha (TNF-alpha) activity. TNF-alpha is probably the most pleiotropic cytokine and, given the deleterious effects to the host of this factor, it has been postulated that its expression must be tightly regulated. Our laboratory has recently isolated, cloned and characterized a novel human transcription factor named LITAF or LPS-induced TNF-alpha factor. The present study reports the isolation, cloning and characterization of the mouse LITAF cDNA. Chromosomal localization revealed that mouse LITAF mapped to mouse chromosome 16, in a region highly homologous with the area on which human LITAF was previously located. Northern blot analysis shows that mouse LITAF is already expressed at embryonic day 7 of development, and is highly expressed in adult liver, heart and kidney. Moreover, upon LPS stimulation, we show that: (i) LITAF expression is increased in a mouse monocyte/macrophage cell line; and (ii) TNF-alpha expression is reduced in ES cell-derived macrophages lacking one copy of LITAF gene. Taken together, these results highlight the important role of LITAF in the regulation of TNF-alpha gene expression and suggest a potential role of LITAF in mouse organogenesis.
对细菌及细菌产物（如脂多糖，LPS）的炎症反应是由多种分泌因子介导的，但LPS的细胞毒性作用被认为归因于肿瘤坏死因子α（TNF-α）的活性。TNF-α可能是最具多效性的细胞因子，鉴于该因子对宿主的有害影响，有人推测其表达必须受到严格调控。我们实验室最近分离、克隆并鉴定了一种名为LITAF或LPS诱导的TNF-α因子的新型人类转录因子。本研究报告了小鼠LITAF cDNA的分离、克隆和鉴定。染色体定位显示，小鼠LITAF定位于小鼠16号染色体，该区域与人类LITAF先前所在区域高度同源。Northern印迹分析表明，小鼠LITAF在发育的胚胎第7天就已表达，在成年肝脏、心脏和肾脏中高表达。此外，在LPS刺激下，我们发现：（i）在小鼠单核细胞/巨噬细胞系中LITAF表达增加；（ii）在缺失一个LITAF基因拷贝的ES细胞衍生的巨噬细胞中TNF-α表达降低。综上所述，这些结果突出了LITAF在TNF-α基因表达调控中的重要作用，并提示LITAF在小鼠器官发生中可能发挥的作用。
