Multiple Cathepsins Promote Pro-IL-1β Synthesis and NLRP3-Mediated IL-1β Activation.

ABSTRACT: Sterile particles induce robust inflammatory responses that underlie the pathogenesis of diseases like silicosis, gout, and atherosclerosis. A key cytokine mediating this response is IL-1β. The generation of bioactive IL-1β by sterile particles is mediated by the NOD-like receptor containing a pyrin domain 3 (NLRP3) inflammasome, although exactly how this occurs is incompletely resolved. Prior studies have found that the cathepsin B inhibitor, Ca074Me, suppresses this response, supporting a model whereby ingested particles disrupt lysosomes and release cathepsin B into the cytosol, somehow activating NLRP3. However, reports that cathepsin B-deficient macrophages have no defect in particle-induced IL-1β generation have questioned cathepsin B's involvement. In this study, we examine the hypo

SUBMITTER: Orlowski GM 

PROVIDER: S-EPMC4530060 | biostudies-literature | 2015 Aug

REPOSITORIES: biostudies-literature