Attenuated inflammatory response of monocyte-derived macrophage from patients with BD : a preliminary report
Autor(a) principal: | |
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Data de Publicação: | 2019 |
Outros Autores: | , , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UFRGS |
Texto Completo: | http://hdl.handle.net/10183/199728 |
Resumo: | Background: Innate immune system dysfunction has been recognized as an important element in the pathophysiology of bipolar disorder (BD). We aimed to investigate whether there are differences in the response of macrophages derived from patients in the early stages and late stages of BD and healthy subjects. Methods: Human monocytes purified from peripheral blood mononuclear cells (PBMCs) of patients with BD type I (n = 18)—further classified into early- and late stage BD patients according to their functioning- and from healthy individuals (n = 10) were differentiated into macrophages in vitro. Monocyte-derived macrophages (M) were exposed to IFNγ plus LPS-M(IFNγ + LPS)- or IL-4-M(IL-4)—to induce their polarization into the classical (also called M1) or alternative (also called M2) activation phenotypes, respectively; or either Mψ were not exposed to any stimuli characterizing the resting state (denominated M0). In vitro secretion of cytokines, such as IL-1β, IL-6, IL-10, and TNF-α, was used as an index of macrophage activity. Results: M(IFNγ + LPS) from late-stage BD patients produced less amount of IL-1β, IL-6, and IL-10 when compared to early-stage BD patients and healthy controls. Following alternative activation, M(IL-4) derived from late-stage patients secreted less IL-6 compared to the other groups. TNFα was less secreted by all macrophage phenotypes derived from late-stage patients when compared to healthy controls only (p < 0.005). Mψ from late-stage patients exhibited lower production of IL-1β and IL-10 compared to macrophages from healthy subjects and early-stage patients respectively. Interestingly, cytokines secretion from M(IFNγ + LPS), M(IL-4) and Mψ were similar between early-stage patients and healthy controls. Conclusion: Our results suggest a progressive dysfunction in the response of peripheral innate immune cells of BD patients in the late stages of the illness. This failure in the regulation of the immune system function may be implicated in the multisystemic progression of BD. |
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Ascoli, Bruna MariaParisi, Mariana MiglioriniBristot, GiovanaPinto, Bárbara AntqueviezcGéa, Luíza PaulColombo, RafaelKapczinski, Flávio PereiraGuma, Fátima Theresinha Costa RodriguesBrietzke, Elisa MacedoBarbé-Tuana, Florencia MaríaRosa, Adriane Ribeiro2019-09-25T03:45:07Z20192194-7511http://hdl.handle.net/10183/199728001100258Background: Innate immune system dysfunction has been recognized as an important element in the pathophysiology of bipolar disorder (BD). We aimed to investigate whether there are differences in the response of macrophages derived from patients in the early stages and late stages of BD and healthy subjects. Methods: Human monocytes purified from peripheral blood mononuclear cells (PBMCs) of patients with BD type I (n = 18)—further classified into early- and late stage BD patients according to their functioning- and from healthy individuals (n = 10) were differentiated into macrophages in vitro. Monocyte-derived macrophages (M) were exposed to IFNγ plus LPS-M(IFNγ + LPS)- or IL-4-M(IL-4)—to induce their polarization into the classical (also called M1) or alternative (also called M2) activation phenotypes, respectively; or either Mψ were not exposed to any stimuli characterizing the resting state (denominated M0). In vitro secretion of cytokines, such as IL-1β, IL-6, IL-10, and TNF-α, was used as an index of macrophage activity. Results: M(IFNγ + LPS) from late-stage BD patients produced less amount of IL-1β, IL-6, and IL-10 when compared to early-stage BD patients and healthy controls. Following alternative activation, M(IL-4) derived from late-stage patients secreted less IL-6 compared to the other groups. TNFα was less secreted by all macrophage phenotypes derived from late-stage patients when compared to healthy controls only (p < 0.005). Mψ from late-stage patients exhibited lower production of IL-1β and IL-10 compared to macrophages from healthy subjects and early-stage patients respectively. Interestingly, cytokines secretion from M(IFNγ + LPS), M(IL-4) and Mψ were similar between early-stage patients and healthy controls. Conclusion: Our results suggest a progressive dysfunction in the response of peripheral innate immune cells of BD patients in the late stages of the illness. This failure in the regulation of the immune system function may be implicated in the multisystemic progression of BD.application/pdfengInternational journal of bipolar disorders. Heidelberg. Vol. 7 (June 2019), 13, 11 p.Transtorno bipolarCitocinasMacrófagosBipolar disorderMood disordersInflammatory cytokinesMacrophage polarizationMacrophage dysfunctionAttenuated inflammatory response of monocyte-derived macrophage from patients with BD : a preliminary reportEstrangeiroinfo:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UFRGSinstname:Universidade Federal do Rio Grande do Sul (UFRGS)instacron:UFRGSTEXT001100258.pdf.txt001100258.pdf.txtExtracted Texttext/plain51283http://www.lume.ufrgs.br/bitstream/10183/199728/2/001100258.pdf.txt29dd92c25282628acb46365cdce60980MD52ORIGINAL001100258.pdfResumoapplication/pdf1034727http://www.lume.ufrgs.br/bitstream/10183/199728/1/001100258.pdf370812ff6954676b2832799a56c04fe9MD5110183/1997282020-01-09 05:01:47.826626oai:www.lume.ufrgs.br:10183/199728Repositório de PublicaçõesPUBhttps://lume.ufrgs.br/oai/requestopendoar:2020-01-09T07:01:47Repositório Institucional da UFRGS - Universidade Federal do Rio Grande do Sul (UFRGS)false |
dc.title.pt_BR.fl_str_mv |
Attenuated inflammatory response of monocyte-derived macrophage from patients with BD : a preliminary report |
title |
Attenuated inflammatory response of monocyte-derived macrophage from patients with BD : a preliminary report |
spellingShingle |
Attenuated inflammatory response of monocyte-derived macrophage from patients with BD : a preliminary report Ascoli, Bruna Maria Transtorno bipolar Citocinas Macrófagos Bipolar disorder Mood disorders Inflammatory cytokines Macrophage polarization Macrophage dysfunction |
title_short |
Attenuated inflammatory response of monocyte-derived macrophage from patients with BD : a preliminary report |
title_full |
Attenuated inflammatory response of monocyte-derived macrophage from patients with BD : a preliminary report |
title_fullStr |
Attenuated inflammatory response of monocyte-derived macrophage from patients with BD : a preliminary report |
title_full_unstemmed |
Attenuated inflammatory response of monocyte-derived macrophage from patients with BD : a preliminary report |
title_sort |
Attenuated inflammatory response of monocyte-derived macrophage from patients with BD : a preliminary report |
author |
Ascoli, Bruna Maria |
author_facet |
Ascoli, Bruna Maria Parisi, Mariana Migliorini Bristot, Giovana Pinto, Bárbara Antqueviezc Géa, Luíza Paul Colombo, Rafael Kapczinski, Flávio Pereira Guma, Fátima Theresinha Costa Rodrigues Brietzke, Elisa Macedo Barbé-Tuana, Florencia María Rosa, Adriane Ribeiro |
author_role |
author |
author2 |
Parisi, Mariana Migliorini Bristot, Giovana Pinto, Bárbara Antqueviezc Géa, Luíza Paul Colombo, Rafael Kapczinski, Flávio Pereira Guma, Fátima Theresinha Costa Rodrigues Brietzke, Elisa Macedo Barbé-Tuana, Florencia María Rosa, Adriane Ribeiro |
author2_role |
author author author author author author author author author author |
dc.contributor.author.fl_str_mv |
Ascoli, Bruna Maria Parisi, Mariana Migliorini Bristot, Giovana Pinto, Bárbara Antqueviezc Géa, Luíza Paul Colombo, Rafael Kapczinski, Flávio Pereira Guma, Fátima Theresinha Costa Rodrigues Brietzke, Elisa Macedo Barbé-Tuana, Florencia María Rosa, Adriane Ribeiro |
dc.subject.por.fl_str_mv |
Transtorno bipolar Citocinas Macrófagos |
topic |
Transtorno bipolar Citocinas Macrófagos Bipolar disorder Mood disorders Inflammatory cytokines Macrophage polarization Macrophage dysfunction |
dc.subject.eng.fl_str_mv |
Bipolar disorder Mood disorders Inflammatory cytokines Macrophage polarization Macrophage dysfunction |
description |
Background: Innate immune system dysfunction has been recognized as an important element in the pathophysiology of bipolar disorder (BD). We aimed to investigate whether there are differences in the response of macrophages derived from patients in the early stages and late stages of BD and healthy subjects. Methods: Human monocytes purified from peripheral blood mononuclear cells (PBMCs) of patients with BD type I (n = 18)—further classified into early- and late stage BD patients according to their functioning- and from healthy individuals (n = 10) were differentiated into macrophages in vitro. Monocyte-derived macrophages (M) were exposed to IFNγ plus LPS-M(IFNγ + LPS)- or IL-4-M(IL-4)—to induce their polarization into the classical (also called M1) or alternative (also called M2) activation phenotypes, respectively; or either Mψ were not exposed to any stimuli characterizing the resting state (denominated M0). In vitro secretion of cytokines, such as IL-1β, IL-6, IL-10, and TNF-α, was used as an index of macrophage activity. Results: M(IFNγ + LPS) from late-stage BD patients produced less amount of IL-1β, IL-6, and IL-10 when compared to early-stage BD patients and healthy controls. Following alternative activation, M(IL-4) derived from late-stage patients secreted less IL-6 compared to the other groups. TNFα was less secreted by all macrophage phenotypes derived from late-stage patients when compared to healthy controls only (p < 0.005). Mψ from late-stage patients exhibited lower production of IL-1β and IL-10 compared to macrophages from healthy subjects and early-stage patients respectively. Interestingly, cytokines secretion from M(IFNγ + LPS), M(IL-4) and Mψ were similar between early-stage patients and healthy controls. Conclusion: Our results suggest a progressive dysfunction in the response of peripheral innate immune cells of BD patients in the late stages of the illness. This failure in the regulation of the immune system function may be implicated in the multisystemic progression of BD. |
publishDate |
2019 |
dc.date.accessioned.fl_str_mv |
2019-09-25T03:45:07Z |
dc.date.issued.fl_str_mv |
2019 |
dc.type.driver.fl_str_mv |
Estrangeiro info:eu-repo/semantics/article |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10183/199728 |
dc.identifier.issn.pt_BR.fl_str_mv |
2194-7511 |
dc.identifier.nrb.pt_BR.fl_str_mv |
001100258 |
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2194-7511 001100258 |
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http://hdl.handle.net/10183/199728 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.ispartof.pt_BR.fl_str_mv |
International journal of bipolar disorders. Heidelberg. Vol. 7 (June 2019), 13, 11 p. |
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openAccess |
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