PuSH - Publication Server of Helmholtz Zentrum München

Mirea, A.M.* ; Stienstra, R.* ; Kanneganti, T.D.* ; Tack, C.J.* ; Chavakis, T. ; Toonen, E.J.M.* ; Joosten, L.A.B.*

Mice deficient in the IL-1β activation genes  Prtn3, Elane, and Casp1 are protected against the development of obesity-induced NAFLD.

Inflammation 43, 1054–1064 (2020)
Publ. Version/Full Text Research data DOI
Open Access Gold (Paid Option)
Creative Commons Lizenzvertrag
Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease. Inflammatory pathways contribute to disease pathogenesis; however, regulation of the underlying mechanism is not completely understood. IL-1β, a pro-inflammatory cytokine, participates in the development and progression of NAFLD. To become bioactive, IL-1β requires enzymatic processing. Mechanisms that activate IL-1β include the classical NLRP3 inflammasome-caspase-1 and the neutrophil serine proteases, neutrophil elastase, and proteinase-3. Several studies have shown that both caspase-1 and the neutrophil serine proteases are important for NAFLD development. However, it is unknown whether these pathways interact and if they have a synergistic effect in promoting NAFLD. In the present study, we developed a novel and unique mouse model by intercrossing caspase-1/11 knockout mice with neutrophil elastase/proteinase-3 double knockout mice. Subsequently, these mice were examined regarding the development of high-fat diet-induced NAFLD. Our results show that mice deficient in caspase-1, neutrophil elastase, and proteinase-3 were protected from developing diet-induced weigh gain, liver steatosis, and adipose tissue inflammation when compared with controls. We conclude that pathways that process pro-IL-1β to bioactive IL-1β play an important role in promoting the development of NAFLD and obesity-induced inflammation. Targeting these pathways could have a therapeutic potential in patients with NAFLD.
Altmetric
Additional Metrics?
Edit extra informations Login
Publication type Article: Journal article
Document type Scientific Article
Keywords Il-1 Beta ; Inflammation ; Neutrophil Serine Proteases ; Obesity
ISSN (print) / ISBN 0360-3997
e-ISSN 1573-2576
Journal Inflammation
Quellenangaben Volume: 43, Issue: , Pages: 1054–1064 Article Number: , Supplement: ,
Publisher Plenum Press
Publishing Place New York
Reviewing status Peer reviewed
Institute(s) Institute for Pancreatic Beta Cell Research (IPI)