Dysregulated NADPH Oxidase Promotes Bone Damage in Murine Model of Autoinflammatory Osteomyelitis
Language English Country England, Great Britain Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
Grant support
P 33000
Austrian Science Fund FWF - Austria
W 1261
Austrian Science Fund FWF - Austria
PubMed
32024700
DOI
10.4049/jimmunol.1900953
PII: jimmunol.1900953
Knihovny.cz E-resources
- MeSH
- Adaptor Proteins, Signal Transducing genetics metabolism MeSH
- Cell Line MeSH
- Cytoskeletal Proteins genetics metabolism MeSH
- Interleukin-1beta immunology metabolism MeSH
- Bone and Bones immunology pathology MeSH
- Humans MeSH
- Disease Models, Animal MeSH
- Mutation MeSH
- Mice, Transgenic MeSH
- Mice MeSH
- NADPH Oxidase 2 genetics metabolism MeSH
- Neutrophils immunology metabolism MeSH
- Osteomyelitis genetics immunology pathology MeSH
- Primary Cell Culture MeSH
- Signal Transduction genetics immunology MeSH
- Superoxides immunology metabolism MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Mice MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Adaptor Proteins, Signal Transducing MeSH
- Cybb protein, mouse MeSH Browser
- Cytoskeletal Proteins MeSH
- IL1B protein, mouse MeSH Browser
- Interleukin-1beta MeSH
- NADPH Oxidase 2 MeSH
- Pstpip2 protein, mouse MeSH Browser
- Superoxides MeSH
Autoinflammatory diseases are characterized by dysregulation of the innate immune system, leading to spontaneous inflammation. Pstpip2cmo mouse strain is a well-characterized model of this class of disorders. Because of the mutation leading to the lack of adaptor protein PSTPIP2, these animals suffer from autoinflammatory chronic multifocal osteomyelitis similar to several human syndromes. Current evidence suggests that it is driven by hyperproduction of IL-1β by neutrophil granulocytes. In this study, we show that in addition to IL-1β, PSTPIP2 also negatively regulates pathways governing reactive oxygen species generation by neutrophil NOX2 NADPH oxidase. Pstpip2cmo neutrophils display highly elevated superoxide production in response to a range of stimuli. Inactivation of NOX2 NADPH oxidase in Pstpip2cmo mice did not affect IL-1β levels, and the autoinflammatory process was initiated with similar kinetics. However, the bone destruction was almost completely alleviated, suggesting that dysregulated NADPH oxidase activity is a key factor promoting autoinflammatory bone damage in Pstpip2cmo mice.
Faculty of Science Charles University 12800 Prague Czech Republic
Max F Perutz Laboratories University of Vienna 1030 Vienna Austria
References provided by Crossref.org
