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AuthorAl-Awad, Duha
AuthorAl-Emadi, Nada
AuthorAbu-Madi, Marawan
AuthorAl-Thani, Asmaa A.
AuthorZughaier, Susu M.
Available date2021-01-05T06:19:05Z
Publication Date2020-12-01
Publication NameBiomedicines
Identifierhttp://dx.doi.org/10.3390/biomedicines8120598
CitationAl-Awad D, Al-Emadi N, Abu-Madi M, Al-Thani AA, Zughaier SM. The Role of Soluble Uric Acid in Modulating Autophagy Flux and Inflammasome Activation during Bacterial Infection in Macrophages. Biomedicines. 2020 Dec 12;8(12):598. doi: 10.3390/biomedicines8120598. PMID: 33322651; PMCID: PMC7763195.
URIhttps://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85097526859&origin=inward
URIhttp://hdl.handle.net/10576/17278
Abstract© 2020 by the authors. Licensee MDPI, Basel, Switzerland. Autophagy is a homeostatic process that regulates and recycles intracellular structures and is a host defense mechanism that facilitates bacterial clearance. Uric acid in plasma is a major antioxidant but in certain conditions acts as an inflammatory danger signal. The aim of this study is to investigate the effect of soluble uric acid on autophagy and the inflammatory responses in macrophages during bacterial infection. Herein, we employed murine RAW264.7 macrophages that express uricase enzyme and human THP-1 cells that are uricase-deficient. Three different strains of Staphylococcus aureus and two different strains of Klebsiella pneumoniae were used to infect macrophages in presence and absence of soluble uric acid. We found that soluble uric acid enhanced autophagy flux in infected macrophages. We observed that IL-1β increased during bacterial infection but decreased when macrophages were co-stimulated with bacteria and uric acid. In contrast to IL-1β, soluble uric acid did not affect TNFα release and there were no dramatic differences when macrophages were infected with S. aureus or K. pneumoniae. In conclusion, uric acid enhances autophagy flux during bacterial infection, consequently reducing inflammasome activation in macrophages. Understanding the effect of uric acid on the interplay between autophagy and inflammation will facilitate therapeutic design.
Languageen
PublisherMDPI
SubjectAutophagy flux
Bacterial infection
Hyperuricemia
IL-1β
Inflammasome
Inflammation
Macrophages
Uric acid
TitleThe role of soluble uric acid in modulating autophagy flux and inflammasome activation during bacterial infection in macrophages
TypeArticle
Issue Number12
Volume Number8
ESSN2227-9059


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