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Lipopolysaccharide-induced inflammation in monocytes/macrophages is blocked by liposomal delivery of G(i)-protein inhibitor

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 G(i) protein in mediating LPS effects has been demonstrated in m...

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Autores principales: Tucureanu, Monica Madalina, Rebleanu, Daniela, Constantinescu, Cristina Ana, Deleanu, Mariana, Voicu, Geanina, Butoi, Elena, Calin, Manuela, Manduteanu, Ileana
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Dove Medical Press 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5743190/
https://www.ncbi.nlm.nih.gov/pubmed/29317816
http://dx.doi.org/10.2147/IJN.S150918
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author Tucureanu, Monica Madalina
Rebleanu, Daniela
Constantinescu, Cristina Ana
Deleanu, Mariana
Voicu, Geanina
Butoi, Elena
Calin, Manuela
Manduteanu, Ileana
author_facet Tucureanu, Monica Madalina
Rebleanu, Daniela
Constantinescu, Cristina Ana
Deleanu, Mariana
Voicu, Geanina
Butoi, Elena
Calin, Manuela
Manduteanu, Ileana
author_sort Tucureanu, Monica Madalina
collection PubMed
description 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 G(i) 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 G(i)-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.
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spelling pubmed-57431902018-01-09 Lipopolysaccharide-induced inflammation in monocytes/macrophages is blocked by liposomal delivery of G(i)-protein inhibitor Tucureanu, Monica Madalina Rebleanu, Daniela Constantinescu, Cristina Ana Deleanu, Mariana Voicu, Geanina Butoi, Elena Calin, Manuela Manduteanu, Ileana Int J Nanomedicine Original Research 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 G(i) 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 G(i)-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. Dove Medical Press 2017-12-20 /pmc/articles/PMC5743190/ /pubmed/29317816 http://dx.doi.org/10.2147/IJN.S150918 Text en © 2018 Tucureanu et al. This work is published and licensed by Dove Medical Press Limited The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.
spellingShingle Original Research
Tucureanu, Monica Madalina
Rebleanu, Daniela
Constantinescu, Cristina Ana
Deleanu, Mariana
Voicu, Geanina
Butoi, Elena
Calin, Manuela
Manduteanu, Ileana
Lipopolysaccharide-induced inflammation in monocytes/macrophages is blocked by liposomal delivery of G(i)-protein inhibitor
title Lipopolysaccharide-induced inflammation in monocytes/macrophages is blocked by liposomal delivery of G(i)-protein inhibitor
title_full Lipopolysaccharide-induced inflammation in monocytes/macrophages is blocked by liposomal delivery of G(i)-protein inhibitor
title_fullStr Lipopolysaccharide-induced inflammation in monocytes/macrophages is blocked by liposomal delivery of G(i)-protein inhibitor
title_full_unstemmed Lipopolysaccharide-induced inflammation in monocytes/macrophages is blocked by liposomal delivery of G(i)-protein inhibitor
title_short Lipopolysaccharide-induced inflammation in monocytes/macrophages is blocked by liposomal delivery of G(i)-protein inhibitor
title_sort lipopolysaccharide-induced inflammation in monocytes/macrophages is blocked by liposomal delivery of g(i)-protein inhibitor
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5743190/
https://www.ncbi.nlm.nih.gov/pubmed/29317816
http://dx.doi.org/10.2147/IJN.S150918
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