beta-Hydroxybutyrate deactivates Neutrophil NLRP3 inflammasome to relieve gout flares [Elektronisk resurs]
-
Goldberg, Emily L. (författare)
-
Asher, Jennifer L. (författare)
-
Molony, Ryan D. (författare)
-
Shaw, Albert C. (författare)
-
Zeiss, Caroline J. (författare)
-
Wang, Chao (författare)
-
Morozova-Roche, Ludmilla A. (författare)
-
Herzog, Raimund I. (författare)
-
Iwasaki, Akiko (författare)
-
Dixit, Vishwa Deep (författare)
-
- Umeå universitet Medicinska fakulteten (utgivare)
-
-
Alternativt namn: Umeå universitet. Medicinsk-odontologiska fakulteten
-
Alternativt namn: Medicinska fakulteten vid Umeå universitet
- 2017
- Engelska.
-
Ingår i: Cell reports. - 2211-1247. ; 18:9, 2077-2087
-
Läs hela texten
-
Läs hela texten
-
Läs hela texten
Sammanfattning
Ämnesord
Stäng
- Aging and lipotoxicity are two major risk factors for gout that are linked by the activation of the NLRP3 inflammasome. Neutrophil-mediated production of interleukin-1 beta (IL-1 beta) drives gouty flares that cause joint destruction, intense pain, and fever. However, metabolites that impact neutrophil inflammasome remain unknown. Here, we identified that ketogenic diet (KD) increases beta-hydroxybutyrate (BHB) and alleviates urate crystal-induced gout without impairing immune defense against bacterial infection. BHB inhibited NLRP3 inflammasome in S100A9 fibril-primed and urate crystal-activated macrophages, which serve to recruit inflammatory neutrophils in joints. Consistent with reduced gouty flares in rats fed a ketogenic diet, BHB blocked IL-1 beta in neutrophils in a NLRP3-dependent manner in mice and humans irrespective of age. Mechanistically, BHB inhibited the NLRP3 inflammasome in neutrophils by reducing priming and assembly steps. Collectively, our studies show that BHB, a known alternate metabolic fuel, is also an anti-inflammatory molecule that may serve as a treatment for gout.
Ämnesord
- Medical and Health Sciences (hsv)
- Basic Medicine (hsv)
- Cell and Molecular Biology (hsv)
- Medicin och hälsovetenskap (hsv)
- Medicinska grundvetenskaper (hsv)
- Cell- och molekylärbiologi (hsv)
- Clinical Medicine (hsv)
- Rheumatology and Autoimmunity (hsv)
- Klinisk medicin (hsv)
- Reumatologi och inflammation (hsv)
Inställningar
Hjälp
Beståndsinformation saknas