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Updated: Dec 29, 2025
Bioluminescence Imaging of NADPH Oxidase Activity in Different Animal Models
Published on: October 22, 2012
Dysregulated NADPH Oxidase Promotes Bone Damage in Murine Model of Autoinflammatory Osteomyelitis
Jarmila Kralova1, Ales Drobek1,2, Jan Prochazka3,4
1Laboratory of Leukocyte Signalling, Institute of Molecular Genetics of the Czech Academy of Sciences, 14220 Prague, Czech Republic.
Abstract:
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.
Insights
Autoinflammatory diseases involve innate immune system dysregulation. In Pstpip2 mice, blocking NADPH oxidase reduced bone damage, revealing its role in autoinflammatory bone destruction.
Area of Science:
- Immunology
- Molecular Biology
- Genetics
Background:
- Autoinflammatory diseases stem from innate immune system dysregulation, causing spontaneous inflammation.
- The Pstpip2(cmo) mouse model exhibits autoinflammatory chronic multifocal osteomyelitis due to a PSTPIP2 adaptor protein deficiency.
- Existing research implicates hyperproduction of IL-1β by neutrophils in this condition.
Purpose of the Study:
- To investigate the role of PSTPIP2 in regulating reactive oxygen species (ROS) generation by neutrophil NOX2 NADPH oxidase.
- To determine the contribution of NOX2 NADPH oxidase activity to the autoinflammatory bone destruction observed in Pstpip2(cmo) mice.
Main Methods:
- Characterization of Pstpip2(cmo) neutrophils for superoxide production.
- Inactivation of NOX2 NADPH oxidase in Pstpip2(cmo) mice.
- Assessment of IL-1β levels and bone destruction kinetics.
Main Results:
- Pstpip2(cmo) neutrophils exhibit significantly elevated superoxide production.
- Inactivating NOX2 NADPH oxidase did not alter IL-1β levels or inflammatory onset.
- Bone destruction was substantially alleviated upon NOX2 NADPH oxidase inactivation.
Conclusions:
- PSTPIP2 negatively regulates ROS generation by neutrophil NOX2 NADPH oxidase.
- Dysregulated NADPH oxidase activity, not IL-1β, is the primary driver of autoinflammatory bone damage in Pstpip2(cmo) mice.
- Targeting NADPH oxidase may offer a therapeutic strategy for autoinflammatory bone diseases.
