Medizin - Open Access LMU - Teil 19/22

Protective and Aggravating Effects of Nlrp3 Inflammasome Activation in IBD Models: Influence of Genetic and Environmental Factors


Listen Later

Background: Inflammatory bowel disease (IBD) is characterized by chronic intestinal inflammation due to dysregulation of the mucosal immune system. The cytokines IL-1 beta and IL-18 appear early in intestinal inflammation and their pro-forms are processed via the caspase-1-activating multiprotein complex, the Nlrp3 inflammasome. Previously, we reported that the uptake of dextran sodium sulfate (DSS) by macrophages activates the Nlrp3 inflammasome and that Nlrp3(-/-) mice are protected in the acute DSS colitis model. Of note, other groups have reported opposing effects in regards to DSS susceptibility in Nlrp3(-/-) mice. Recently, mice lacking inflammasomes were found to develop a distinct intestinal microflora. Methods: To reconcile the contradicting observations, we investigated the role of Nlrp3 deficiency in two different IBD models: acute DSS colitis and TNBS (2,4,6-trinitrobenzene sulfonic acid)-induced colitis. In addition, we in-vestigated the impact of the intestinal flora on disease severity by performing cohousing experiments of wild-type and Nlrp3(-/-) mice, as well as by antibiotic treatment. Results: Nlrp3(-/-) mice treated with either DSS or TNBS exhibited attenuated colitis and lower mortality. This protective effect correlated with an increased frequency of CD103+ lamina propria dendritic cells expressing a tolerogenic phenotype in Nlrp3(-/-) mice in steady state conditions. Interestingly, after cohousing, Nlrp3(-/-) mice were as susceptible as wild-type mice, indicating that transmission of endogenous bacterial flora between the two mouse strains might increase susceptibility of Nlrp3(-/-) mice towards DSS-induced colitis. Accordingly, treatment with antibiotics almost completely prevented colitis in the DSS model. Conclusions: The composition of the intestinal microflora significantly influences disease severity in IBD models comparing wild-type and Nlrp3(-/-) mice. This observation may - at least in part - explain contradictory results concerning the role of the inflammasome in different labs. Further studies are required to define the role of the Nlrp3 inflammasome in noninflamed mucosa under steady state conditions and in IBD. Copyright (C) 2012 S. Karger AG, Basel
...more
View all episodesView all episodes
Download on the App Store

Medizin - Open Access LMU - Teil 19/22By Ludwig-Maximilians-Universität München


More shows like Medizin - Open Access LMU - Teil 19/22

View all
In search of dark matter by Prof. Dr. Andreas Burkert

In search of dark matter

0 Listeners

Theoretical Physics Schools (ASC) by The Arnold Sommerfeld Center for Theoretical Physics (ASC)

Theoretical Physics Schools (ASC)

2 Listeners

MCMP – Mathematical Philosophy (Archive 2011/12) by MCMP Team

MCMP – Mathematical Philosophy (Archive 2011/12)

6 Listeners

Hegel lectures by Robert Brandom, LMU Munich by Robert Brandom, Axel Hutter

Hegel lectures by Robert Brandom, LMU Munich

6 Listeners

MCMP – Philosophy of Science by MCMP Team

MCMP – Philosophy of Science

1 Listeners

MCMP – Logic by MCMP Team

MCMP – Logic

2 Listeners

Epistemology and Philosophy of Science: Prof. Dr. Stephan Hartmann – HD by Ludwig-Maximilians-Universität München

Epistemology and Philosophy of Science: Prof. Dr. Stephan Hartmann – HD

1 Listeners

ISCB34 - 34th Annual Conference of the International Society for Clinical Biostatistics - Munich, 25-29 August 2013 by Prof. Dr. rer. nat. Ulrich Mansmann

ISCB34 - 34th Annual Conference of the International Society for Clinical Biostatistics - Munich, 25-29 August 2013

0 Listeners

MCMP – Philosophy of Physics by MCMP Team

MCMP – Philosophy of Physics

3 Listeners

LMU An introduction to Bohmian Mechanics by Florian Hoffmann und Nicola Vona

LMU An introduction to Bohmian Mechanics

2 Listeners