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.
- MeSH
- adaptorové proteiny signální transdukční genetika metabolismus MeSH
- buněčné linie MeSH
- cytoskeletální proteiny genetika metabolismus MeSH
- interleukin-1beta imunologie metabolismus MeSH
- kosti a kostní tkáň imunologie patologie MeSH
- lidé MeSH
- modely nemocí na zvířatech MeSH
- mutace MeSH
- myši transgenní MeSH
- myši MeSH
- NADPH-oxidasa 2 genetika metabolismus MeSH
- neutrofily imunologie metabolismus MeSH
- osteomyelitida genetika imunologie patologie MeSH
- primární buněčná kultura MeSH
- signální transdukce genetika imunologie MeSH
- superoxidy imunologie metabolismus MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
