Dysregulated NADPH Oxidase Promotes Bone Damage in Murine Model of Autoinflammatory Osteomyelitis
Identifikátory výsledku
Kód výsledku v IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68378050%3A_____%2F20%3A00525175" target="_blank" >RIV/68378050:_____/20:00525175 - isvavai.cz</a>
Nalezeny alternativní kódy
RIV/00216208:11310/20:10422358
Výsledek na webu
<a href="https://www.jimmunol.org/content/204/6/1607" target="_blank" >https://www.jimmunol.org/content/204/6/1607</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.4049/jimmunol.1900953" target="_blank" >10.4049/jimmunol.1900953</a>
Alternativní jazyky
Jazyk výsledku
angličtina
Název v původním jazyce
Dysregulated NADPH Oxidase Promotes Bone Damage in Murine Model of Autoinflammatory Osteomyelitis
Popis výsledku v původním jazyce
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.
Název v anglickém jazyce
Dysregulated NADPH Oxidase Promotes Bone Damage in Murine Model of Autoinflammatory Osteomyelitis
Popis výsledku anglicky
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.
Klasifikace
Druh
J<sub>imp</sub> - Článek v periodiku v databázi Web of Science
CEP obor
—
OECD FORD obor
30102 - Immunology
Návaznosti výsledku
Projekt
Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.
Návaznosti
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Ostatní
Rok uplatnění
2020
Kód důvěrnosti údajů
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Údaje specifické pro druh výsledku
Název periodika
Journal of Immunology
ISSN
0022-1767
e-ISSN
—
Svazek periodika
204
Číslo periodika v rámci svazku
6
Stát vydavatele periodika
US - Spojené státy americké
Počet stran výsledku
19
Strana od-do
1607-1620
Kód UT WoS článku
000519583700019
EID výsledku v databázi Scopus
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