Scharte Marion, Jurk Kerstin, Kehrel Beate, Zarbock Alexander, Van Aken Hugo, Singbartl Kai
Klinik und Poliklinik für Anästhesiologie und operative Intensivmedizin, Universitätsklinikum Münster, Germany.
FEBS Lett. 2006 Nov 27;580(27):6399-404. doi: 10.1016/j.febslet.2006.10.053. Epub 2006 Nov 3.
Hypoxia-inducible factor-1 (HIF-1) is a transcription factor that mediates the adaptive response to hypoxia. Increasing evidence suggests a crucial role for HIF-1 in immune reactions. Here we investigated the effect of the Th2 type cytokines IL-4 and IL-10 on HIF-1alpha mediated response in normoxia (21% O2) and hypoxia (1% O2). Incubation of human transformed intestinal cells (HT-29) with IL-4 significantly increased HIF-1alpha protein levels during hypoxia but not during normoxia. Mechanisms involved are IL-4 induced up-regulation of HIF-1alpha gene transcription and the PI3K signaling pathway. The increase in hypoxia-induced accumulation of HIF-1alpha protein after IL-4 treatment did not result in up-regulation of HIF-1 DNA-binding activity or HIF-1 dependent gene expression. IL-10 did not affect HIF-1alpha protein levels.
缺氧诱导因子-1（HIF-1）是一种介导对缺氧适应性反应的转录因子。越来越多的证据表明HIF-1在免疫反应中起关键作用。在此，我们研究了Th2型细胞因子白细胞介素-4（IL-4）和白细胞介素-10（IL-10）对常氧（21%氧气）和缺氧（1%氧气）条件下HIF-1α介导反应的影响。用IL-4孵育人转化肠细胞（HT-29），在缺氧而非常氧期间显著增加了HIF-1α蛋白水平。涉及的机制是IL-4诱导HIF-1α基因转录上调以及磷脂酰肌醇-3激酶（PI3K）信号通路。IL-4处理后缺氧诱导的HIF-1α蛋白积累增加并未导致HIF-1 DNA结合活性或HIF-1依赖性基因表达上调。IL-10不影响HIF-1α蛋白水平。
