The gut microbiota metabolite urolithin A inhibits NF-κB activation in LPS stimulated BMDMs

Abstract Inflammation is a natural defense process of the innate immune system, associated with the release of proinflammatory cytokines such as interleukin-1β, interleukin-6, interleukin-12 and TNFα; and enzymes including iNOS through the activation and nuclear translocation of NF-κB p65 due to the...

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Autores principales:	Khalid N. M. Abdelazeem, M. Zaher Kalo, Sandra Beer-Hammer, Florian Lang
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/2d205e2815f3417bb5b7973a0f995ea1
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spelling	oai:doaj.org-article:2d205e2815f3417bb5b7973a0f995ea12021-12-02T14:23:32ZThe gut microbiota metabolite urolithin A inhibits NF-κB activation in LPS stimulated BMDMs10.1038/s41598-021-86514-62045-2322https://doaj.org/article/2d205e2815f3417bb5b7973a0f995ea12021-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-86514-6https://doaj.org/toc/2045-2322Abstract Inflammation is a natural defense process of the innate immune system, associated with the release of proinflammatory cytokines such as interleukin-1β, interleukin-6, interleukin-12 and TNFα; and enzymes including iNOS through the activation and nuclear translocation of NF-κB p65 due to the phosphorylation of IκBα. Regulation of intracellular Ca2+ is considered a promising strategy for the prevention of reactive oxygen species (ROS) production and accumulation of DNA double strand breaks (DSBs) that occurs in inflammatory-associated-diseases. Among the metabolites of ellagitannins that are produced in the gut microbiome, urolithin A (UA) has received an increasing attention as a novel candidate with anti-inflammatory and anti-oxidant effects. Here, we investigated the effect of UA on the suppression of pro-inflammatory molecules and NF-κB activation by targeting TLR4 signalling pathway. We also identified the influence of UA on Ca2+ entry, ROS production and DSBs availability in murine bone-marrow-derived macrophages challenged with lipopolysaccharides (LPS). We found that UA inhibits IκBα phosphorylation and supresses MAPK and PI3K activation. In addition, UA was able to reduce calcium entry, ROS production and DSBs availability. In conclusion, we suggest that urolithin A is a promising therapeutic agent for treating inflammatory diseases through suppression of NF-κB and preserving DNA through maintaining intracellular calcium and ROS homeostasis.Khalid N. M. AbdelazeemM. Zaher KaloSandra Beer-HammerFlorian LangNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-16 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Khalid N. M. Abdelazeem M. Zaher Kalo Sandra Beer-Hammer Florian Lang The gut microbiota metabolite urolithin A inhibits NF-κB activation in LPS stimulated BMDMs
description	Abstract Inflammation is a natural defense process of the innate immune system, associated with the release of proinflammatory cytokines such as interleukin-1β, interleukin-6, interleukin-12 and TNFα; and enzymes including iNOS through the activation and nuclear translocation of NF-κB p65 due to the phosphorylation of IκBα. Regulation of intracellular Ca2+ is considered a promising strategy for the prevention of reactive oxygen species (ROS) production and accumulation of DNA double strand breaks (DSBs) that occurs in inflammatory-associated-diseases. Among the metabolites of ellagitannins that are produced in the gut microbiome, urolithin A (UA) has received an increasing attention as a novel candidate with anti-inflammatory and anti-oxidant effects. Here, we investigated the effect of UA on the suppression of pro-inflammatory molecules and NF-κB activation by targeting TLR4 signalling pathway. We also identified the influence of UA on Ca2+ entry, ROS production and DSBs availability in murine bone-marrow-derived macrophages challenged with lipopolysaccharides (LPS). We found that UA inhibits IκBα phosphorylation and supresses MAPK and PI3K activation. In addition, UA was able to reduce calcium entry, ROS production and DSBs availability. In conclusion, we suggest that urolithin A is a promising therapeutic agent for treating inflammatory diseases through suppression of NF-κB and preserving DNA through maintaining intracellular calcium and ROS homeostasis.
format	article
author	Khalid N. M. Abdelazeem M. Zaher Kalo Sandra Beer-Hammer Florian Lang
author_facet	Khalid N. M. Abdelazeem M. Zaher Kalo Sandra Beer-Hammer Florian Lang
author_sort	Khalid N. M. Abdelazeem
title	The gut microbiota metabolite urolithin A inhibits NF-κB activation in LPS stimulated BMDMs
title_short	The gut microbiota metabolite urolithin A inhibits NF-κB activation in LPS stimulated BMDMs
title_full	The gut microbiota metabolite urolithin A inhibits NF-κB activation in LPS stimulated BMDMs
title_fullStr	The gut microbiota metabolite urolithin A inhibits NF-κB activation in LPS stimulated BMDMs
title_full_unstemmed	The gut microbiota metabolite urolithin A inhibits NF-κB activation in LPS stimulated BMDMs
title_sort	gut microbiota metabolite urolithin a inhibits nf-κb activation in lps stimulated bmdms
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/2d205e2815f3417bb5b7973a0f995ea1
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The gut microbiota metabolite urolithin A inhibits NF-κB activation in LPS stimulated BMDMs

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