Developmental endothelial locus‐1 (Del‐1) antagonizes Interleukin‐17‐mediated allergic asthma.

Abstract: Interleukin (IL)‐17 is a major contributor to the pathogenesis of allergic asthma. Developmental endothelial locus‐1 (Del‐1) is an endothelial cell‐secreted protein known to inhibit IL‐17 expression. However, little is known about the association between Del‐1 and IL‐17 in the pathogenesis of allergic asthma. Using bronchoalveolar lavage fluid (BALF) and peripheral blood samples collected from allergic asthmatic patients and controls, we explored the role of Del‐1 in relation to IL‐17 in allergic asthma. We found that the negative correlation between Del‐1 and IL‐17 was significant in BALF of allergic asthmatics. Del‐1 treatment inhibited the expression of IL‐17, the differentiation of IL‐17‐secreting leukocytes and associated cytokines. Contrarily, IL‐17 levels were increased after treatment with anti‐Del‐1 mAb. Consistent with this, Del‐1 treatment led to downregulation of IL‐5, CCL5 and IL‐4, thus reducing secretion of eosinophil cationic protein. Furthermore, Del‐1 significantly downregulated the expression of ICAM‐1 and may have the potential to reduce leukocyte transendothelial migration. Our data demonstrate that Del‐1 can negatively regulate IL‐17 and its proinflammatory function, thereby limiting airway inflammation in allergic asthmatics, and suggest Del‐1 as a potential candidate for prevention and treatment of allergic asthma. [ABSTRACT FROM AUTHOR]