Increased serum soluble vascular endothelial cadherin levels in patients with chronic spontaneous urticaria

Abstract

BackgroundChronic spontaneous urticaria (CSU) is a common skin disease characterized by recurrent itchy wheals with or without angioedema that lasts longer than 6 weeks. Vascular endothelial (VE)-cadherin is an endothelial cell-specific adhesion molecule that plays critical roles in angiogenesis and endothelial permeability. ObjectiveTo investigate serum levels of soluble VE (sVE)-cadherin in patients with CSU. MethodsSerum levels of sVE-cadherin in patients with CSU, patients with atopic dermatitis, and healthy controls were determined by enzyme-linked immunosorbent assay. In addition, changes in sVE-cadherin serum levels were compared in patients with CSU before and after H1 antihistamine treatment. Furthermore, the effects of histamine on sVE-cadherin release by HMEC-1 cells were determined by enzyme-linked immunosorbent assay. The inhibition effects of H1 antihistamine and H2 antihistamine on sVE-cadherin release, VE-cadherin phosphorylation, and VE-cadherin disruption were evaluated in histamine-treated HMEC-1 cells by western blot and immunofluorescence. ResultsSerum levels of sVE-cadherin in patients with CSU were significantly higher than those in patients with atopic dermatitis and healthy controls. Serum sVE-cadherin levels in patients with CSU were correlated with the severity of CSU according to Urticaria Activity Scores. Furthermore, serum sVE-cadherin levels in patients with CSU at pretreatment decreased after H1 antihistamine treatment. In addition, histamine markedly induced sVE-cadherin release in HMEC-1 cells. Moreover, H1 antihistamine, but not H2 antihistamine, significantly inhibited sVE-cadherin release in histamine-treated HMEC-1 cells. Western blot data showed that histamine induced phosphorylation of VE-cadherin in HMEC-1 cells, which was blocked by H1 antihistamine. ConclusionThe present data showed serum levels of sVE-cadherin are increased in patients with CSU. Histamine-induced sVE-cadherin release from endothelial cells could play a role in the pathogenesis of CSU.