Dysregulated NADPH Oxidase Promotes Bone Damage in Murine Model of Autoinflammatory Osteomyelitis

0525175 - ÚMG 2021 RIV US eng J - Journal Article
Králová, Jarmila - Drobek, Aleš - Procházka, Jan - Špoutil, František - Fabišik, Matěj - Glatzová, Daniela - Borna, Šimon - Pokorná, Jana - Skopcová, Tereza - Angelisová, Pavla - Gregor, Martin - Kovařík, P. - Sedláček, Radislav - Brdička, Tomáš
Dysregulated NADPH Oxidase Promotes Bone Damage in Murine Model of Autoinflammatory Osteomyelitis.
Journal of Immunology. Roč. 204, č. 6 (2020), s. 1607-1620. ISSN 0022-1767. E-ISSN 1550-6606
R&D Projects: GA MŠMT(CZ) LM2015040; GA MŠMT(CZ) LQ1604; GA MŠMT ED2.1.00/19.0395; GA MŠMT LO1419; GA MŠMT(CZ) LM2015062; GA MŠMT(CZ) ED1.1.00/02.0109; GA MŠMT EF16_013/0001789; GA MŠMT(CZ) EF16_013/0001775; GA MŠMT LO1220; GA ČR(CZ) GA17-07155S
Institutional support: RVO:68378050
Keywords : inflammasome activation * molecular-mechanisms * periodic syndromes * oxidative stress * disease * innate * immune * pstpip2 * family * phosphorylation
OECD category: Immunology
Impact factor: 5.422, year: 2020
Method of publishing: Open access with time embargo
https://www.jimmunol.org/content/204/6/1607

Autoinflammatory diseases are characterized by dysregulation of the innate immune system, leading to spontaneous inflammation. Pstpip2(cmo) 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-1 beta by neutrophil granulocytes. In this study, we show that in addition to IL-1 beta, PSTPIP2 also negatively regulates pathways governing reactive oxygen species generation by neutrophil NOX2 NADPH oxidase. Pstpip2(cmo) neutrophils display highly elevated superoxide production in response to a range of stimuli. Inactivation of NOX2 NADPH oxidase in Pstpip2(cmo) mice did not affect IL-1 beta 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 Pstpip2(cmo) mice.
Permanent Link: http://hdl.handle.net/11104/0309376