Fiche publication
Date publication
janvier 2020
Journal
Frontiers in cell and developmental biology
Auteurs
Membres identifiés du Cancéropôle Est :
Pr GHIRINGHELLI François
,
Dr REBE Cédric
,
Dr CHALMIN Fanny
,
Dr DERANGERE Valentin
Tous les auteurs :
Chevriaux A, Pilot T, Derangère V, Simonin H, Martine P, Chalmin F, Ghiringhelli F, Rébé C
Lien Pubmed
Résumé
The mechanisms leading to NOD-leucine rich repeat and pyrin containing protein 3 (NLRP3) inflammasome activation are still debated. It is well established that oligomerized NLRP3 interacts with apoptosis associated Speck-like protein containing a CARD domain (ASC) which polymerizes into filaments recruiting procaspase-1, leading to its activation. However, pathways triggering NLRP3 activation, such as potassium efflux, ROS production or lysosomal permeabilization, can be required or not, depending on the activators used. Here we proposed to evaluate the importance of Cathepsin B on NLRP3 inflammasome assembly and activation. Using Cathepsin B BMDMs (Bone Marrow-Derived Macrophages), we first show that Cathepsin B is required for caspase-1 activation, IL-1β production and ASC speck formation, upon treatment with different types of NLRP3 activators, i.e., ATP, nigericin or crystals. Moreover, in these conditions, Cathepsin B interacts with NLRP3 at the endoplasmic reticulum (ER) level. To conclude, different NLRP3 activators lead to Cathepsin B interaction with NLRP3 at the ER level and to subsequent caspase-1 activation.
Mots clés
Cathepsin B, IL-1β, NLRP3, caspase-1, macrophages
Référence
Front Cell Dev Biol. 2020 ;8:167
