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• W2884458341 abstract "Background and Purpose Allergic conjunctivitis is an eye inflammation that involves the infiltration of immune cells into the conjunctiva via cell surface‐adhesion receptors, such as integrin α 4 β 1 . These receptors interact with adhesion molecules expressed on the conjunctival endothelium and may be a target to treat this disease. We synthesized DS‐70, a novel α/β‐peptidomimetic α 4 integrin antagonist, to prevent the conjunctival infiltration of immune cells and clinical symptoms in a model of allergic conjunctivitis. Experimental Approach In vitro, DS‐70 was pharmacologically characterized using a scintillation proximity procedure to measure its affinity for α 4 β 1 integrin, and its effect on cell adhesion mediated by different integrins was also evaluated. The effects of DS‐70 on vascular cell adhesion molecule‐1 (VCAM‐1)‐mediated degranulation of a human mast cell line and an eosinophilic cell line, which both express α 4 β 1 , and on VCAM‐1‐mediated phosphorylation of ERK 1/2 in Jurkat E6.1 cells were investigated. Effects of DS‐70 administered in the conjunctival fornix of ovalbumin‐sensitized guinea pigs were evaluated. Key Results DS‐70 bound to integrin α 4 β 1 with nanomolar affinity, prevented the adhesion of α 4 integrin‐expressing cells, antagonized VCAM‐1‐mediated degranulation of mast cells and eosinophils and ERK 1/2 phosphorylation. Only 20% was degraded after an 8 h incubation with serum. DS‐70 dose‐dependently reduced the clinical symptoms of allergic conjunctivitis, conjunctival α 4 integrin expression and conjunctival levels of chemokines and cytokines in ovalbumin‐sensitized guinea pigs. Conclusions and Implications These findings highlight the role of α 4 integrin in allergic conjunctivitis and suggest that DS‐70 is a potential treatment for this condition." @default.
• W2884458341 created "2018-08-03" @default.
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• W2884458341 date "2018-09-17" @default.
• W2884458341 modified "2023-09-26" @default.
• W2884458341 title "DS-70, a novel and potent α₄ integrin antagonist, is an effective treatment for experimental allergic conjunctivitis in guinea pigs" @default.
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• W2884458341 doi "https://doi.org/10.1111/bph.14458" @default.
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