A mouse model of MSU-induced acute inflammation suggests imiquimod-dependent targeting of as relevant therapy for gout patients.
Fiche publication
Date publication
janvier 2020
Journal
Theranostics
Auteurs
Membres identifiés du Cancéropôle Est :
Pr BAHRAM Siamak, Dr FRISCH Benoit, Dr CARAPITO Raphaël, Dr PO Chrystelle
Tous les auteurs :
Mariotte A, De Cauwer A, Po C, Abou-Faycal C, Pichot A, Paul N, Aouadi I, Carapito R, Frisch B, Macquin C, Chatelus E, Sibilia J, Armspach JP, Bahram S, Georgel P
Lien Pubmed
Résumé
: The role of Monosodium Urate (MSU) crystals in gout pathophysiology is well described, as is the major impact of IL-1β in the inflammatory reaction that constitutes the hallmark of the disease. However, despite the discovery of the NLRP3 inflammasome and its role as a Pattern Recognition Receptor linking the detection of a danger signal (MSU) to IL-1β secretion , the precise mechanisms leading to joint inflammation in gout patients are still poorly understood. : Acute urate crystal inflammation was obtained by subcutaneous injections of MSU crystals in mice. Symptoms were followed by scoring, cytokine quantification by ELISA and western blot, gene expression by RT-qPCR and RNAseq; Magnetic Resonance Imaging was also used to assess inflammation. : We provide an extensive clinical, biological and molecular characterization of an acute uratic inflammation mouse model which accurately mimics human gout. We report the efficacy of topical imiquimod treatment and its impact on Interferon-dependent down modulation of gene expression in this experimental model. : Our work reveals several key features of MSU-dependent inflammation and identifies novel therapeutic opportunities for gout patients.
Référence
Theranostics. 2020 ;10(5):2158-2171