Implication of REDD1 in the activation of inflammatory pathways

Abstract In response to endotoxemia, the organism triggers an inflammatory response, and the visceral adipose tissue represents a major source of proinflammatory cytokines. The regulation of inflammation response in the adipose tissue is thus of crucial importance. We demonstrated that Regulated in...

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Autores principales:	Faustine Pastor, Karine Dumas, Marie-Astrid Barthélémy, Claire Regazzetti, Noémie Druelle, Pascal Peraldi, Mireille Cormont, Jean-François Tanti, Sophie Giorgetti-Peraldi
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/ef7e6eae90454a8ba2c1f73c9ea64b63
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spelling	oai:doaj.org-article:ef7e6eae90454a8ba2c1f73c9ea64b632021-12-02T15:05:57ZImplication of REDD1 in the activation of inflammatory pathways10.1038/s41598-017-07182-z2045-2322https://doaj.org/article/ef7e6eae90454a8ba2c1f73c9ea64b632017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-07182-zhttps://doaj.org/toc/2045-2322Abstract In response to endotoxemia, the organism triggers an inflammatory response, and the visceral adipose tissue represents a major source of proinflammatory cytokines. The regulation of inflammation response in the adipose tissue is thus of crucial importance. We demonstrated that Regulated in development and DNA damage response-1 (REDD1) is involved in inflammation. REDD1 expression was increased in response to lipopolysaccharide (LPS) in bone marrow derived macrophages (BMDM) and in epidydimal adipose tissue. Loss of REDD1 protected the development of inflammation, since the expression of proinflammatory cytokines (TNFα, IL-6, IL-1β) was decreased in adipose tissue of REDD1−/− mice injected with LPS compared to wild-type mice. This decrease was associated with an inhibition of the activation of p38MAPK, JNK, NF-κB and NLRP3 inflammasome leading to a reduction of IL-1β secretion in response to LPS and ATP in REDD1−/− BMDM. Although REDD1 is an inhibitor of mTORC1, loss of REDD1 decreased inflammation independently of mTORC1 activation but more likely through oxidative stress regulation. Absence of REDD1 decreases ROS associated with a dysregulation of Nox-1 and GPx3 expression. Absence of REDD1 in macrophages decreases the development of insulin resistance in adipocyte-macrophage coculture. Altogether, REDD1 appears to be a key player in the control of inflammation.Faustine PastorKarine DumasMarie-Astrid BarthélémyClaire RegazzettiNoémie DruellePascal PeraldiMireille CormontJean-François TantiSophie Giorgetti-PeraldiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-12 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Faustine Pastor Karine Dumas Marie-Astrid Barthélémy Claire Regazzetti Noémie Druelle Pascal Peraldi Mireille Cormont Jean-François Tanti Sophie Giorgetti-Peraldi Implication of REDD1 in the activation of inflammatory pathways
description	Abstract In response to endotoxemia, the organism triggers an inflammatory response, and the visceral adipose tissue represents a major source of proinflammatory cytokines. The regulation of inflammation response in the adipose tissue is thus of crucial importance. We demonstrated that Regulated in development and DNA damage response-1 (REDD1) is involved in inflammation. REDD1 expression was increased in response to lipopolysaccharide (LPS) in bone marrow derived macrophages (BMDM) and in epidydimal adipose tissue. Loss of REDD1 protected the development of inflammation, since the expression of proinflammatory cytokines (TNFα, IL-6, IL-1β) was decreased in adipose tissue of REDD1−/− mice injected with LPS compared to wild-type mice. This decrease was associated with an inhibition of the activation of p38MAPK, JNK, NF-κB and NLRP3 inflammasome leading to a reduction of IL-1β secretion in response to LPS and ATP in REDD1−/− BMDM. Although REDD1 is an inhibitor of mTORC1, loss of REDD1 decreased inflammation independently of mTORC1 activation but more likely through oxidative stress regulation. Absence of REDD1 decreases ROS associated with a dysregulation of Nox-1 and GPx3 expression. Absence of REDD1 in macrophages decreases the development of insulin resistance in adipocyte-macrophage coculture. Altogether, REDD1 appears to be a key player in the control of inflammation.
format	article
author	Faustine Pastor Karine Dumas Marie-Astrid Barthélémy Claire Regazzetti Noémie Druelle Pascal Peraldi Mireille Cormont Jean-François Tanti Sophie Giorgetti-Peraldi
author_facet	Faustine Pastor Karine Dumas Marie-Astrid Barthélémy Claire Regazzetti Noémie Druelle Pascal Peraldi Mireille Cormont Jean-François Tanti Sophie Giorgetti-Peraldi
author_sort	Faustine Pastor
title	Implication of REDD1 in the activation of inflammatory pathways
title_short	Implication of REDD1 in the activation of inflammatory pathways
title_full	Implication of REDD1 in the activation of inflammatory pathways
title_fullStr	Implication of REDD1 in the activation of inflammatory pathways
title_full_unstemmed	Implication of REDD1 in the activation of inflammatory pathways
title_sort	implication of redd1 in the activation of inflammatory pathways
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/ef7e6eae90454a8ba2c1f73c9ea64b63
work_keys_str_mv	AT faustinepastor implicationofredd1intheactivationofinflammatorypathways AT karinedumas implicationofredd1intheactivationofinflammatorypathways AT marieastridbarthelemy implicationofredd1intheactivationofinflammatorypathways AT claireregazzetti implicationofredd1intheactivationofinflammatorypathways AT noemiedruelle implicationofredd1intheactivationofinflammatorypathways AT pascalperaldi implicationofredd1intheactivationofinflammatorypathways AT mireillecormont implicationofredd1intheactivationofinflammatorypathways AT jeanfrancoistanti implicationofredd1intheactivationofinflammatorypathways AT sophiegiorgettiperaldi implicationofredd1intheactivationofinflammatorypathways
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Implication of REDD1 in the activation of inflammatory pathways

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