Inhibiting the immunoproteasome's β5i catalytic activity affects human peripheral blood-derived immune cell viability.

ABSTRACT: Small molecule inhibitors selectively targeting the immunoproteasome subunit β5i are currently being developed for the treatment of autoimmune disorders. However, patients carrying loss-of-function mutations in the gene encoding β5i (Psmb8) suffer from the proteasome-associated autoinflammatory syndromes (PRAAS) emphasizing the need to study pharmacological inhibition of immunoproteasome function in human cells. Here, we characterized the immunomodulatory potential of the selective β5i inhibitor ONX 0914 and Bortezomib, a pan-proteasome inhibitor, in human peripheral blood mononuclear cells (PBMCs). Both compounds efficiently blocked pro-inflammatory cytokine secretion in human whole blood and PBMC cultures stimulated with toll-like receptor (TLR) agonists. Furthermore, the compounds inhib

SUBMITTER: Pletinckx K 

PROVIDER: S-EPMC6581949 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature