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  • Goldberg, Emily L. (author)

beta-Hydroxybutyrate deactivates Neutrophil NLRP3 inflammasome to relieve gout flares

  • Article/chapterEnglish2017

Publisher, publication year, extent ...

  • Elsevier BV,2017
  • electronicrdacarrier

Numbers

  • LIBRIS-ID:oai:DiVA.org:umu-133663
  • https://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-133663URI
  • https://doi.org/10.1016/j.celrep.2017.02.004DOI

Supplementary language notes

  • Language:English
  • Summary in:English

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  • Subject category:ref swepub-contenttype
  • Subject category:art swepub-publicationtype

Notes

  • 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.

Subject headings and genre

Added entries (persons, corporate bodies, meetings, titles ...)

  • Asher, Jennifer L. (author)
  • Molony, Ryan D. (author)
  • Shaw, Albert C. (author)
  • Zeiss, Caroline J. (author)
  • Wang, ChaoUmeå universitet,Institutionen för medicinsk kemi och biofysik(Swepub:umu)chwa0028 (author)
  • Morozova-Roche, Ludmilla A.Umeå universitet,Institutionen för medicinsk kemi och biofysik(Swepub:umu)lumo0001 (author)
  • Herzog, Raimund I. (author)
  • Iwasaki, Akiko (author)
  • Dixit, Vishwa Deep (author)
  • Umeå universitetInstitutionen för medicinsk kemi och biofysik (creator_code:org_t)

Related titles

  • In:Cell Reports: Elsevier BV18:9, s. 2077-20872211-1247

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