Untersuchungen zum Inflammasom bei proinflammatorischem Zellstress des Muskels in vitro und in vivo

Analysis of the inflammasome due to proinflammatory cell stress in vitro and in vivo

by Imke Bertram
Doctoral thesis
Date of Examination:2021-07-29
Date of issue:2021-07-12
Advisor:PD Dr. Jens Schmidt
Referee:PD Dr. Fred Lühder
Referee:Prof. Dr. Thomas Meyer
Persistent Address: http://dx.doi.org/10.53846/goediss-8709

 

 

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Abstract

English

The inclusion body myositis (IBM) is the most common acquired inflammatory myopathy with an onset of the disease from the age of 50. With a combination of degeneration and inflammation it is unique within the group of idiopathic inflammatory myopathies. There has been a description of some links between both pathways, but most of the pathogenesis remains unclear. Earlier findings show that endogenous cell stress and protein accumulation function as activators of pro-inflammatory protein complexes and also being found within biopsies of IBM patients, it seems to be a natural approach to detect the inflammasome as link between inflammation and degeneration within IBM pathogenesis. Using a well-developed cell culture model of chronic muscle inflammation as well as muscle biopsies of IBM patients compared to a non-inflammatory control group, the work’s results show a relevant upregulation of NLRP3 due to inflammatory cell stress. Additionally, an upregulation of genes with synergistic effects on the NLRP3 inflammasome, MHC-I expression and T-cell migration is present in biopsies of IBM patients. Biopsies of patients with dermatomyositis, polymyositis, necrotizing myopathy and muscular dystrophies have also been examined on same targets. The results of this work support the hypothesis that NLRP3 and upregulated synergistic protein complexes are another link between inflammation and degeneration within IBM pathogenesis.
Keywords: NLRP3; Inflammasome; IBM
Schlagwörter: Einschlusskörpermyositis; IBM; NLRP3; Inflammasom
 
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