RAGE-dependent VCAM-1 expression in the lung endothelium mediates IL-33-induced allergic airway inflammation.

BACKGROUND:The receptor for advanced glycation endproducts has been implicated as a critical molecule in the pathogenesis of experimental asthma/allergic airway inflammation (AAI). It has been previously shown that acts both upstream of interleukin-33 (IL-33) release and downstream of IL-33 release via IL-33-induced accumulation of type 2 innate lymphoid cells (ILC2s) in the lungs, which perpetuate type 2 inflammation and mucus metaplasia. However, the mechanism by which duanyu1648 mediates downstream IL-33-induced type 2 inflammatory responses is unknown. OBJECTIVE:This study tested the hypothesis that ILC2s are recruited to the lungs via duanyu1648-dependent vascular cell adhesion molecule 1 (VCAM-1) expression on lung endothelial cells. METHODS:House dust mite extract, Alternaria alternata extract, or rIL-33 was used to induce AAI/VCAM-1 expression in wild-type (WT) and mice. Intravenous (i.v.) anti-VCAM-1 or intraperitoneal (i.p.) β7 blocking antibody administration was used to determine the role of VCAM-1 in IL-33-induced AAI. RESULTS:Enhanced VCAM-1 expression in the lungs by HDM, AA, or rIL-33 exposure was found to be In addition, stimulation of primary mouse lung endothelial cells with IL-33 induced VCAM-1 expression in WT, but not cells. Administration of VCAM-1 and β7-integrin blocking antibodies reduced IL-33-induced eosinophilic inflammation, mucus metaplasia, and type 2 inflammatory responses. CONCLUSION:This study demonstrates that allergen- and cytokine-induced VCAM-1 expression is duanyu1648-dependent and contributes to lung ILC2 accumulation and downstream eosinophilic inflammation, mucus metaplasia, and type 2 inflammatory responses.

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