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.
Department of Periodontology, School of Dentistry, Aichigakuin University, Nagoya 464-8650, Japan.
Megumi
M
Inomata
Takeshi
T
Into
Misako
M
Nakashima
Toshihide
T
Noguchi
Kenji
K
Matsushita
D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D015847:Interleukin-4 / Q000494:pharmacology*; D009928:Organ Specificity; D019007:P-Selectin / Q000378:metabolism; D050800:STAT6 Transcription Factor / Q000378:metabolism*; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000378:metabolism*; D020302:Weibel-Palade Bodies / Q000187:drug effects* / Q000235:genetics*
D019007:P-Selectin; C108944:SOCS1 protein, human; D050800:STAT6 Transcription Factor; C494101:STAT6 protein, human; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D015847:Interleukin-4