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• W2807743335 abstract "Abstract Background The receptor for advanced glycation endproducts ( RAGE ) has been implicated as a critical molecule in the pathogenesis of experimental asthma/allergic airway inflammation ( AAI ). It has been previously shown that RAGE acts both upstream of interleukin‐33 ( IL ‐33) release and downstream of IL ‐33 release via RAGE ‐dependent IL ‐33‐induced accumulation of type 2 innate lymphoid cells ( ILC 2s) in the lungs, which perpetuate type 2 inflammation and mucus metaplasia. However, the mechanism by which RAGE mediates downstream IL ‐33‐induced type 2 inflammatory responses is unknown. Objective This study tested the hypothesis that ILC 2s are recruited to the lungs via RAGE ‐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 RAGE ‐knockout ( RAGE ‐ KO ) 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 RAGE ‐dependent. In addition, stimulation of primary mouse lung endothelial cells with IL ‐33 induced VCAM ‐1 expression in WT , but not RAGE ‐ KO 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 RAGE ‐dependent and contributes to lung ILC 2 accumulation and downstream eosinophilic inflammation, mucus metaplasia, and type 2 inflammatory responses." @default.
• W2807743335 created "2018-06-21" @default.
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• W2807743335 date "2018-11-22" @default.
• W2807743335 modified "2023-10-15" @default.
• W2807743335 title "<scp>RAGE</scp>‐dependent<scp>VCAM</scp>‐1 expression in the lung endothelium mediates<scp>IL</scp>‐33‐induced allergic airway inflammation" @default.
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• W2807743335 doi "https://doi.org/10.1111/all.13500" @default.
• W2807743335 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/29900561" @default.
• W2807743335 hasPublicationYear "2018" @default.
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