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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...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Dove Medical Press
2017
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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. |
format | Online Article Text |
id | pubmed-5743190 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Dove Medical Press |
record_format | MEDLINE/PubMed |
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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