IL-4 and IL-13 activate the JAK2 tyrosine kinase and Stat6 in cultured human vascular endothelial cells through a common pathway that does not involve the γ(c) chain

Abstract

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 g(c), the common signaling subunit of the IL-2, IL-4, IL-7, IL-9, and IL-15 receptors, or through a g(c)-independent pathway that may be alternatively activated by IL-13. We find that human ECs do not express g(c), 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 orgy, and uses JAK2-Stat6 signaling.