Presenting Author: Laura Orellano
, Post Doc Associate at UMass Chan Med. Sch.
Abstract:
In gout patients, MSU crystals formed in the joints cause inflammation, and the activation of the NLRP3 inflammasome is believed to mediate these responses. Cathepsins play an important role in crystal-induced NLRP3 activation that results in subsequent speck formation, caspase-1 activation, IL-1β secretion, and pyroptosis. In this study, we investigated if cathepsins can also influence MSU-induced NLRP3 activation in a gout mouse model. VBY-825 is a reversible pan-cathepsin inhibitor, and we found that VBY-825 significantly suppressed IL-1β secretion and LDH levels from peritoneal naïve macrophages upon MSU stimulation in vito. In a mouse peritonitis model, we found that VBY-825 suppressed MSU-induced inflammation when compared to the control treatment. Interestingly, the inflammation demonstrated by histology and MPO activity in the joints was also reduced by VBY-825 treatment in MSU-induced arthritis. These findings suggest that cathepsins play a critical role in MSU-induced inflammation and could potentially be a target for gout treatment.
Therapeutic potential of VBY-825 in MSU crystal-induced NLRP3 inflammasome activation
Category
Poster and Podium (Block Symposium)
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Date: May 4 Presentation Time: 03:15 PM to 04:30 PM Room: Exhibit Hall F1