IL-4 alters expression patterns of storage components of vascular endothelial cell-specific granules through STAT6- and SOCS-1-dependent mechanisms

IL-4 develops Th2-biased immunity or allergic inflammation through activation of STAT6-dependent signaling. In vascular endothelial cells (ECs), IL-4 elicits regulatory effects on chemokine production and adhesion molecule expression to recruit T cells and eosinophils. In this study, we examined how IL-4 affects Weibel-Palade bodies (WPBs), EC-specific storage granules capable to store multiple protein components, including von Willebrand factor (vWF), P-selectin, eotaxin-3, IL-8 and angiopoietin-2 (Ang-2). Among 11 WPB component genes that we examined, IL-4 potently upregulated the expression levels of P-selectin and eotaxin-3, whereas it downregulated the expression levels of IL-8 and Ang-2. Both regulatory effects were dependent on STAT6. In addition, the IL-4-induced downregulatory effect on WPB component genes depended on the negative feedback regulation by SOCS-1 induced by STAT6 signaling. Furthermore, IL-4-regulated gene expression through STAT6 and SOCS-1 was consistent with WPB compositional changes in cultivated ECs and capillary-like tube networks. Since WPBs enable ECs to rapidly regulate multiple critical functions of vasculatures, IL-4-induced alteration of expression patterns of WPB storage components may convert the physiological functions of WPBs into Th2-biased immune functions or allergic functions.