Lukashev Dmitriy, Sitkovsky Michail
New England Inflammation and Tissue Protection Institute, Northeastern University, Boston, MA, USA.
Hum Immunol. 2008 Jul;69(7):421-5. doi: 10.1016/j.humimm.2008.05.004. Epub 2008 Jun 11.
Hypoxia-inducible factor-1alpha (HIF-1alpha) is critical not only in the regulation of oxygen homeostasis but also in the regulation of innate and adaptive immune systems. We previously reported that T-cell receptor-mediated activation of T cells in mice leads to the expression of an alternative isoform of HIF-1alpha that inhibits activated T cells in a delayed negative feed-back manner. In this paper, we describe a novel mRNA isoform of human HIF-1alpha that is upregulated in peripheral T lymphocytes after T-cell receptor stimulation. This activation- inducible isoform is expressed using the alternative first exon I.3, and it encodes a protein that is 24 amino acids longer than the ubiquitous HIF-1alpha isoform. This mRNA isoform I.3 of HIF-1alpha is expressed in a tissue-specific manner with the highest expression found in peripheral blood leukocytes and the thymus.
缺氧诱导因子-1α（HIF-1α）不仅在氧稳态调节中起关键作用，在固有免疫系统和适应性免疫系统调控中也发挥重要作用。我们之前报道过，小鼠体内T细胞受体介导的T细胞激活会导致一种HIF-1α异构体的表达，该异构体以延迟性负反馈方式抑制活化的T细胞。在本文中，我们描述了一种人类HIF-1α的新型mRNA异构体，其在T细胞受体刺激后的外周T淋巴细胞中上调表达。这种激活诱导型异构体使用替代性第一外显子I.3进行表达，它编码的蛋白质比普遍存在的HIF-1α异构体长24个氨基酸。HIF-1α的这种mRNA异构体I.3以组织特异性方式表达，在外周血白细胞和胸腺中表达量最高。
