Viemann Dorothee, Goebeler Matthias, Schmid Sybille, Klimmek Kerstin, Sorg Clemens, Ludwig Stephan, Roth Johannes
Department of Experimental Dermatology, University Hospital Münster, Muenster, Germany.
Blood. 2004 May 1;103(9):3365-73. doi: 10.1182/blood-2003-09-3296. Epub 2004 Jan 8.
Inflammatory stimulation of endothelial cells by tumor necrosis factor alpha (TNF-alpha) involves activation of nuclear factor kappa B (NF-kappa B) and p38 mitogen-activated protein (MAP) kinase signaling pathways. A reliable analysis of the gene expression program elicited by TNF-alpha and its assignment to distinct signaling pathways is not available. A sophisticated analysis of oligonucleotide microarrays covering more than 13 000 genes allowed definition of the TNF-alpha-regulated endothelial gene expression profile and novel TNF-alpha-induced genes. Virtually all TNF-alpha-inducible genes were dependent on I kappa B kinase 2 (IKK2)/NF-kappa B activation, whereas a minor number was additionally modulated by p38. Furthermore, genes suppressed by IKK2/NF-kappa B were newly identified. Real-time reverse transcriptase-polymerase chain reaction (RT-PCR) and flow cytometry confirmed reliability of data. Thus, these results define a list of primary candidates for targeted modulation of endothelial functions during inflammation.
肿瘤坏死因子α（TNF-α）对内皮细胞的炎症刺激涉及核因子κB（NF-κB）和p38丝裂原活化蛋白（MAP）激酶信号通路的激活。目前尚无对TNF-α引发的基因表达程序及其在不同信号通路中的分配进行可靠分析的方法。对覆盖超过13000个基因的寡核苷酸微阵列进行的复杂分析，使得能够定义TNF-α调节的内皮基因表达谱以及新的TNF-α诱导基因。几乎所有TNF-α诱导的基因都依赖于IκB激酶2（IKK2）/NF-κB的激活，而少数基因还受到p38的额外调节。此外，还新鉴定了受IKK2/NF-κB抑制的基因。实时逆转录聚合酶链反应（RT-PCR）和流式细胞术证实了数据的可靠性。因此，这些结果确定了炎症期间内皮功能靶向调节的主要候选基因清单。
