ASC Specks as a Sizable Contribution to Chronic Inflammation

In this study, we tested the therapeutic potential of VHHASC and a newly generated VHH against murine ASC (VHHmASC) to target ASC specks in vitro and in vivo. We show that pre-incubation of extracellular ASC specks with VHHASC abrogated their inflammatory functions in vitro. Recombinant VHHASC rapidly disassembled pre-formed ASC specks and thus inhibited their ability to seed the nucleation of soluble ASC. Notably, VHHASC required prior cytosolic access to prevent inflammasome activation within cells, but it was effective against extracellular ASC specks released following caspase-1-dependent loss of membrane integrity, and pyroptosis. Finally, systemic treatment with VHHmASC efficiently dampened the inflammation in mouse models of acute gout or chronic rheumatoid arthritis (RA).
Source: Fight Aging! - Category: Research Authors: Tags: Medicine, Biotech, Research Source Type: blogs