Palmer-Crocker R L, Hughes C C, Pober J S
Boyer Center for Molecular Medicine, Yale University School of Medicine, New Haven, Connecticut 06536-0812, USA.
J Clin Invest. 1996 Aug 1;98(3):604-9. doi: 10.1172/JCI118829.
IL-4 and IL-13 each act on human endothelial cells (ECs) to induce expression of vascular cell adhesion molecule-1. On hematopoietic cells. IL-4 responses may be mediated either through a pathway involving gc, the common signaling subunit of the IL-2, IL-4, IL-7, IL-9, and IL-15 receptors, or through a gc-independent pathway that may be alternatively activated by IL-13. We find that human ECs do not express gc, as detected by indirect immunofluorescence and FACS analysis or by a reverse transcription-PCR method. Like IL-4, IL-13 activates a protein tyrosine kinase that phosphorylates the IL-4R binding protein. In addition, we find that IL-4 and IL-13 each induce tyrosine phosphorylation of the JAK2 tyrosine kinase. Furthermore, both IL-4 and IL-13 induce binding of the Stat6 transcription factor to a consensus sequence oligonucleotide. We conclude that the IL-4 response of human ECs involves the IL-13 shared pathway that is independent of gc, and uses JAK2-Stat6 signaling.
白细胞介素-4（IL-4）和白细胞介素-13（IL-13）均可作用于人类内皮细胞（ECs），诱导血管细胞黏附分子-1的表达。在造血细胞上，IL-4的反应可能通过一条涉及γc（IL-2、IL-4、IL-7、IL-9和IL-15受体的共同信号亚基）的途径介导，或者通过一条可被IL-13选择性激活的不依赖γc的途径介导。我们发现，通过间接免疫荧光和荧光激活细胞分选（FACS）分析或逆转录-聚合酶链反应（RT-PCR）方法检测，人类ECs不表达γc。与IL-4一样，IL-13激活一种可使IL-4R结合蛋白磷酸化的蛋白酪氨酸激酶。此外，我们发现IL-4和IL-13均可诱导JAK2酪氨酸激酶的酪氨酸磷酸化。而且，IL-4和IL-13均可诱导信号转导和转录激活因子6（Stat6）转录因子与共有序列寡核苷酸结合。我们得出结论，人类ECs的IL-4反应涉及不依赖γc的IL-13共享途径，并利用JAK2-Stat6信号传导。
