Lipopolysaccharide-induced inflammation in monocytes/macrophages is blocked by liposomal delivery of Gi-protein inhibitor

Monica Madalina Tucureanu,1,* Daniela Rebleanu,1,* Cristina Ana Constantinescu,1,2 Mariana Deleanu,3,4 Geanina Voicu,1 Elena Butoi,1 Manuela Calin,1 Ileana Manduteanu1 1Department of Biopathology and Therapy of Inflammation, Nicolae Simionescu Institute of Cellular Biology and Pathology, Bucharest,...

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Autores principales:	Tucureanu MM, Rebleanu D, Constantinescu CA, Deleanu M, Voicu G, Butoi E, Calin M, Manduteanu I
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2017
Materias:	Guanosine 5’-O-(2-thiodiphosphate) (GOT) MAPK activation cytokine monocyte adhesion chemotaxis. Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/aaeef246e0be49ac9c7502a761c2ba1e
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spelling	oai:doaj.org-article:aaeef246e0be49ac9c7502a761c2ba1e2021-12-02T01:32:47ZLipopolysaccharide-induced inflammation in monocytes/macrophages is blocked by liposomal delivery of Gi-protein inhibitor1178-2013https://doaj.org/article/aaeef246e0be49ac9c7502a761c2ba1e2017-12-01T00:00:00Zhttps://www.dovepress.com/lipopolysaccharide-induced-inflammation-in-monocytesmacrophages-is-blo-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Monica Madalina Tucureanu,1,* Daniela Rebleanu,1,* Cristina Ana Constantinescu,1,2 Mariana Deleanu,3,4 Geanina Voicu,1 Elena Butoi,1 Manuela Calin,1 Ileana Manduteanu1 1Department of Biopathology and Therapy of Inflammation, Nicolae Simionescu Institute of Cellular Biology and Pathology, Bucharest, Romania; 2Faculty of Veterinary Medicine, University of Agronomic Sciences and Veterinary Medicine, Bucharest, Romania; 3Department of Lipidomics, Nicolae Simionescu Institute of Cellular Biology and Pathology, Bucharest, Romania; 4Faculty of Biotechnologies, University of Agronomic Sciences and Veterinary Medicine, Bucharest, Romania *These authors contributed equally to this work Background: Lipopolysaccharide (LPS) is widely recognized as a potent activator of monocytes/macrophages, and its effects include an altered production of key mediators, such as inflammatory cytokines and chemokines. The involvement of Gi protein in mediating LPS effects has been demonstrated in murine macrophages and various cell types of human origin. Purpose: The aim of the present work was to evaluate the potential of a Gi-protein inhibitor encapsulated in liposomes in reducing the inflammatory effects induced by LPS in monocytes/macrophages. Materials and methods: Guanosine 5´-O-(2-thiodiphosphate) (GOT), a guanosine diphosphate analog that completely inhibits G-protein activation by guanosine triphosphate and its analogs, was encapsulated into liposomes and tested for anti-inflammatory effects in LPS-activated THP1 monocytes or THP1-derived macrophages. The viability of monocytes/macrophages after incubation with different concentrations of free GOT or liposome-encapsulated GOT was assessed by MTT assay. MAPK activation and production of IL1β, TNFα, IL6, and MCP1 were assessed in LPS-activated monocytes/macrophages in the presence or absence of free or encapsulated GOT. In addition, the effect of free or liposome-encapsulated GOT on LPS-stimulated monocyte adhesion to activated endothelium and on monocyte chemotaxis was evaluated. Results: We report here that GOT-loaded liposomes inhibited activation of MAPK and blocked the production of the cytokines IL1β, TNFα, IL6, and MCP1 induced by LPS in monocytes and macrophages. Moreover, GOT encapsulated in liposomes reduced monocyte adhesion and chemotaxis. All demonstrated events were in contrast with free GOT, which showed reduced or no effect on monocyte/macrophage activation with LPS. Conclusion: This study demonstrates the potential of liposomal GOT in blocking LPS proinflammatory effects in monocytes/macrophages. Keywords: guanosine 5´-O-(2-thiodiphosphate) (GOT), MAPK activation, cytokine, monocyte adhesion, chemotaxisTucureanu MMRebleanu DConstantinescu CADeleanu MVoicu GButoi ECalin MManduteanu IDove Medical PressarticleGuanosine 5’-O-(2-thiodiphosphate) (GOT)MAPK activationcytokinemonocyte adhesionchemotaxis.Medicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 13, Pp 63-76 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Guanosine 5’-O-(2-thiodiphosphate) (GOT) MAPK activation cytokine monocyte adhesion chemotaxis. Medicine (General) R5-920
spellingShingle	Guanosine 5’-O-(2-thiodiphosphate) (GOT) MAPK activation cytokine monocyte adhesion chemotaxis. Medicine (General) R5-920 Tucureanu MM Rebleanu D Constantinescu CA Deleanu M Voicu G Butoi E Calin M Manduteanu I Lipopolysaccharide-induced inflammation in monocytes/macrophages is blocked by liposomal delivery of Gi-protein inhibitor
description	Monica Madalina Tucureanu,1,* Daniela Rebleanu,1,* Cristina Ana Constantinescu,1,2 Mariana Deleanu,3,4 Geanina Voicu,1 Elena Butoi,1 Manuela Calin,1 Ileana Manduteanu1 1Department of Biopathology and Therapy of Inflammation, Nicolae Simionescu Institute of Cellular Biology and Pathology, Bucharest, Romania; 2Faculty of Veterinary Medicine, University of Agronomic Sciences and Veterinary Medicine, Bucharest, Romania; 3Department of Lipidomics, Nicolae Simionescu Institute of Cellular Biology and Pathology, Bucharest, Romania; 4Faculty of Biotechnologies, University of Agronomic Sciences and Veterinary Medicine, Bucharest, Romania *These authors contributed equally to this work Background: Lipopolysaccharide (LPS) is widely recognized as a potent activator of monocytes/macrophages, and its effects include an altered production of key mediators, such as inflammatory cytokines and chemokines. The involvement of Gi protein in mediating LPS effects has been demonstrated in murine macrophages and various cell types of human origin. Purpose: The aim of the present work was to evaluate the potential of a Gi-protein inhibitor encapsulated in liposomes in reducing the inflammatory effects induced by LPS in monocytes/macrophages. Materials and methods: Guanosine 5´-O-(2-thiodiphosphate) (GOT), a guanosine diphosphate analog that completely inhibits G-protein activation by guanosine triphosphate and its analogs, was encapsulated into liposomes and tested for anti-inflammatory effects in LPS-activated THP1 monocytes or THP1-derived macrophages. The viability of monocytes/macrophages after incubation with different concentrations of free GOT or liposome-encapsulated GOT was assessed by MTT assay. MAPK activation and production of IL1β, TNFα, IL6, and MCP1 were assessed in LPS-activated monocytes/macrophages in the presence or absence of free or encapsulated GOT. In addition, the effect of free or liposome-encapsulated GOT on LPS-stimulated monocyte adhesion to activated endothelium and on monocyte chemotaxis was evaluated. Results: We report here that GOT-loaded liposomes inhibited activation of MAPK and blocked the production of the cytokines IL1β, TNFα, IL6, and MCP1 induced by LPS in monocytes and macrophages. Moreover, GOT encapsulated in liposomes reduced monocyte adhesion and chemotaxis. All demonstrated events were in contrast with free GOT, which showed reduced or no effect on monocyte/macrophage activation with LPS. Conclusion: This study demonstrates the potential of liposomal GOT in blocking LPS proinflammatory effects in monocytes/macrophages. Keywords: guanosine 5´-O-(2-thiodiphosphate) (GOT), MAPK activation, cytokine, monocyte adhesion, chemotaxis
format	article
author	Tucureanu MM Rebleanu D Constantinescu CA Deleanu M Voicu G Butoi E Calin M Manduteanu I
author_facet	Tucureanu MM Rebleanu D Constantinescu CA Deleanu M Voicu G Butoi E Calin M Manduteanu I
author_sort	Tucureanu MM
title	Lipopolysaccharide-induced inflammation in monocytes/macrophages is blocked by liposomal delivery of Gi-protein inhibitor
title_short	Lipopolysaccharide-induced inflammation in monocytes/macrophages is blocked by liposomal delivery of Gi-protein inhibitor
title_full	Lipopolysaccharide-induced inflammation in monocytes/macrophages is blocked by liposomal delivery of Gi-protein inhibitor
title_fullStr	Lipopolysaccharide-induced inflammation in monocytes/macrophages is blocked by liposomal delivery of Gi-protein inhibitor
title_full_unstemmed	Lipopolysaccharide-induced inflammation in monocytes/macrophages is blocked by liposomal delivery of Gi-protein inhibitor
title_sort	lipopolysaccharide-induced inflammation in monocytes/macrophages is blocked by liposomal delivery of gi-protein inhibitor
publisher	Dove Medical Press
publishDate	2017
url	https://doaj.org/article/aaeef246e0be49ac9c7502a761c2ba1e
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Lipopolysaccharide-induced inflammation in monocytes/macrophages is blocked by liposomal delivery of Gi-protein inhibitor

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