Macrophage M1 polarization mediated via the IL-6/STAT3 pathway contributes to apical periodontitis induced by Porphyromonas gingivalis

Objective: To investigate the involvement of IL-6/STAT3 signaling pathway activation in macrophage polarization and bone destruction related to apical periodontitis (AP) stimulated by Porphyromonas gingivalis. Methodology: Macrophage polarization, IL-6/STAT3 expression, and the presence of P. gingiv...

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Autores: Chen, Xuan, Dou, Jinge, Fu, Zhuohui, Qiu, Yang, Zou, Ling, Huang, Dingming, Tan, Xuelian
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2022
País:Brasil
Institución:Universidade de São Paulo (USP)
Repositorio:Journal of applied oral science (Online)
Idioma:inglés
OAI Identifier:oai:revistas.usp.br:article/205823
Acceso en línea:https://www.revistas.usp.br/jaos/article/view/205823
Access Level:acceso abierto
Palabra clave:IL-6/STAT3
Macrophage
Porphyromonas gingivalis
Apical periodontitis
Bone lesion
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spelling Macrophage M1 polarization mediated via the IL-6/STAT3 pathway contributes to apical periodontitis induced by Porphyromonas gingivalisIL-6/STAT3MacrophagePorphyromonas gingivalisApical periodontitisBone lesionObjective: To investigate the involvement of IL-6/STAT3 signaling pathway activation in macrophage polarization and bone destruction related to apical periodontitis (AP) stimulated by Porphyromonas gingivalis. Methodology: Macrophage polarization, IL-6/STAT3 expression, and the presence of P. gingivalis were detected in human AP tissues via RT-qPCR, western blotting, and immunohistochemistry staining. Murine bone marrow derived macrophages were isolated and cultured with P. gingivalis W83 in vitro, and levels of macrophage IL-6 expression, STAT3 phosphorylation, and macrophage polarization with or without the selective STAT3 phosphorylation inhibitor Stattic (5 μM) were detected via ELISA, western blotting, RT-qPCR, and flow cytometry, respectively. P. gingivalis-induced murine AP models were constructed, and bone destruction and macrophage polarization in the apical region were evaluated. Transwell co-culture systems were used to investigate the effects of macrophages infected with P. gingivalis on osteogenesis and osteoclastogenesis. Results: P. gingivalis was detected in human AP tissues that highly expressed IL-6/STAT3, and the M1 subtype of macrophages was more abundant in these tissues. P. gingivalis infection induced IL-6 expression, STAT3 phosphorylation, and M1 polarization of macrophages, while 5 μM of Stattic partially abolished these activation effects. Systemic STAT3 blockade via oral administration of Stattic at a dose of 25 mg kg-1 alleviated murine periapical bone resorption and apical infiltration of M1 macrophages induced by P. gingivalis infection in vivo. Furthermore, macrophages infected with P. gingivalis promoted bone destruction via secretion of IL-6, TNF-α, and RANKL, which hinder pre-osteoblast expression of Runx2 and accelerate pre-osteoclast expression of NFAT2. Conclusions:The activation of IL-6/STAT3 signaling pathway is involved in mediating macrophages M1 polarization in the P. gingivalis induced apical inflammatory context and may also be intimately involved in the bone loss caused by P. gingivalis infection, directing the M1 macrophage infiltration during the progression of AP. Universidade de São Paulo. Faculdade de Odontologia de Bauru2022-12-14info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://www.revistas.usp.br/jaos/article/view/20582310.1590/1678-7757-2022-0316Journal of Applied Oral Science; Vol. 30 (2022); e20220316Journal of Applied Oral Science; Vol. 30 (2022); e20220316Journal of Applied Oral Science; v. 30 (2022); e202203161678-77651678-7757reponame:Journal of applied oral science (Online)instname:Universidade de São Paulo (USP)instacron:USPenghttps://www.revistas.usp.br/jaos/article/view/205823/189332Copyright (c) 2022 Journal of Applied Oral Sciencehttp://creativecommons.org/licenses/by/4.0info:eu-repo/semantics/openAccessChen, XuanDou, JingeFu, ZhuohuiQiu, YangZou, LingHuang, DingmingTan, Xuelian2022-12-14T19:08:03Zoai:revistas.usp.br:article/205823Revistahttp://www.scielo.br/jaosPUBhttps://www.revistas.usp.br/jaos/oai||jaos@usp.br1678-77651678-7757opendoar:2022-12-14T19:08:03Journal of applied oral science (Online) - Universidade de São Paulo (USP)false
dc.title.none.fl_str_mv Macrophage M1 polarization mediated via the IL-6/STAT3 pathway contributes to apical periodontitis induced by Porphyromonas gingivalis
title Macrophage M1 polarization mediated via the IL-6/STAT3 pathway contributes to apical periodontitis induced by Porphyromonas gingivalis
spellingShingle Macrophage M1 polarization mediated via the IL-6/STAT3 pathway contributes to apical periodontitis induced by Porphyromonas gingivalis
Chen, Xuan
IL-6/STAT3
Macrophage
Porphyromonas gingivalis
Apical periodontitis
Bone lesion
title_short Macrophage M1 polarization mediated via the IL-6/STAT3 pathway contributes to apical periodontitis induced by Porphyromonas gingivalis
title_full Macrophage M1 polarization mediated via the IL-6/STAT3 pathway contributes to apical periodontitis induced by Porphyromonas gingivalis
title_fullStr Macrophage M1 polarization mediated via the IL-6/STAT3 pathway contributes to apical periodontitis induced by Porphyromonas gingivalis
title_full_unstemmed Macrophage M1 polarization mediated via the IL-6/STAT3 pathway contributes to apical periodontitis induced by Porphyromonas gingivalis
title_sort Macrophage M1 polarization mediated via the IL-6/STAT3 pathway contributes to apical periodontitis induced by Porphyromonas gingivalis
dc.creator.none.fl_str_mv Chen, Xuan
Dou, Jinge
Fu, Zhuohui
Qiu, Yang
Zou, Ling
Huang, Dingming
Tan, Xuelian
author Chen, Xuan
author_facet Chen, Xuan
Dou, Jinge
Fu, Zhuohui
Qiu, Yang
Zou, Ling
Huang, Dingming
Tan, Xuelian
author_role author
author2 Dou, Jinge
Fu, Zhuohui
Qiu, Yang
Zou, Ling
Huang, Dingming
Tan, Xuelian
author2_role author
author
author
author
author
author
dc.subject.por.fl_str_mv IL-6/STAT3
Macrophage
Porphyromonas gingivalis
Apical periodontitis
Bone lesion
topic IL-6/STAT3
Macrophage
Porphyromonas gingivalis
Apical periodontitis
Bone lesion
description Objective: To investigate the involvement of IL-6/STAT3 signaling pathway activation in macrophage polarization and bone destruction related to apical periodontitis (AP) stimulated by Porphyromonas gingivalis. Methodology: Macrophage polarization, IL-6/STAT3 expression, and the presence of P. gingivalis were detected in human AP tissues via RT-qPCR, western blotting, and immunohistochemistry staining. Murine bone marrow derived macrophages were isolated and cultured with P. gingivalis W83 in vitro, and levels of macrophage IL-6 expression, STAT3 phosphorylation, and macrophage polarization with or without the selective STAT3 phosphorylation inhibitor Stattic (5 μM) were detected via ELISA, western blotting, RT-qPCR, and flow cytometry, respectively. P. gingivalis-induced murine AP models were constructed, and bone destruction and macrophage polarization in the apical region were evaluated. Transwell co-culture systems were used to investigate the effects of macrophages infected with P. gingivalis on osteogenesis and osteoclastogenesis. Results: P. gingivalis was detected in human AP tissues that highly expressed IL-6/STAT3, and the M1 subtype of macrophages was more abundant in these tissues. P. gingivalis infection induced IL-6 expression, STAT3 phosphorylation, and M1 polarization of macrophages, while 5 μM of Stattic partially abolished these activation effects. Systemic STAT3 blockade via oral administration of Stattic at a dose of 25 mg kg-1 alleviated murine periapical bone resorption and apical infiltration of M1 macrophages induced by P. gingivalis infection in vivo. Furthermore, macrophages infected with P. gingivalis promoted bone destruction via secretion of IL-6, TNF-α, and RANKL, which hinder pre-osteoblast expression of Runx2 and accelerate pre-osteoclast expression of NFAT2. Conclusions:The activation of IL-6/STAT3 signaling pathway is involved in mediating macrophages M1 polarization in the P. gingivalis induced apical inflammatory context and may also be intimately involved in the bone loss caused by P. gingivalis infection, directing the M1 macrophage infiltration during the progression of AP. 
publishDate 2022
dc.date.none.fl_str_mv 2022-12-14
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv https://www.revistas.usp.br/jaos/article/view/205823
10.1590/1678-7757-2022-0316
url https://www.revistas.usp.br/jaos/article/view/205823
identifier_str_mv 10.1590/1678-7757-2022-0316
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv https://www.revistas.usp.br/jaos/article/view/205823/189332
dc.rights.driver.fl_str_mv Copyright (c) 2022 Journal of Applied Oral Science
http://creativecommons.org/licenses/by/4.0
info:eu-repo/semantics/openAccess
rights_invalid_str_mv Copyright (c) 2022 Journal of Applied Oral Science
http://creativecommons.org/licenses/by/4.0
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Universidade de São Paulo. Faculdade de Odontologia de Bauru
publisher.none.fl_str_mv Universidade de São Paulo. Faculdade de Odontologia de Bauru
dc.source.none.fl_str_mv Journal of Applied Oral Science; Vol. 30 (2022); e20220316
Journal of Applied Oral Science; Vol. 30 (2022); e20220316
Journal of Applied Oral Science; v. 30 (2022); e20220316
1678-7765
1678-7757
reponame:Journal of applied oral science (Online)
instname:Universidade de São Paulo (USP)
instacron:USP
instname_str Universidade de São Paulo (USP)
instacron_str USP
institution USP
reponame_str Journal of applied oral science (Online)
collection Journal of applied oral science (Online)
repository.name.fl_str_mv Journal of applied oral science (Online) - Universidade de São Paulo (USP)
repository.mail.fl_str_mv ||jaos@usp.br
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score 15,301629

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