Macrophage M1 polarization mediated via the IL-6/STAT3 pathway contributes to apical periodontitis induced by Porphyromonas gingivalis
Abstract 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 o...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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University of São Paulo
2022-11-01
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| Series: | Journal of Applied Oral Science |
| Subjects: | |
| Online Access: | http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1678-77572022000100445&lng=en&tlng=en |
| _version_ | 1811319059145293824 |
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| author | Xuan Chen Jinge Dou Zhuohui Fu Yang Qiu Ling Zou Dingming Huang Xuelian Tan |
| author_facet | Xuan Chen Jinge Dou Zhuohui Fu Yang Qiu Ling Zou Dingming Huang Xuelian Tan |
| author_sort | Xuan Chen |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-04-13T12:36:41Z |
| format | Article |
| id | doaj.art-bf5afb0a0208434bbc191e57c5a11649 |
| institution | Directory Open Access Journal |
| issn | 1678-7765 |
| language | English |
| last_indexed | 2024-04-13T12:36:41Z |
| publishDate | 2022-11-01 |
| publisher | University of São Paulo |
| record_format | Article |
| series | Journal of Applied Oral Science |
| spelling | doaj.art-bf5afb0a0208434bbc191e57c5a116492022-12-22T02:46:39ZengUniversity of São PauloJournal of Applied Oral Science1678-77652022-11-013010.1590/1678-7757-2022-0316Macrophage M1 polarization mediated via the IL-6/STAT3 pathway contributes to apical periodontitis induced by Porphyromonas gingivalisXuan ChenJinge DouZhuohui FuYang QiuLing ZouDingming Huanghttps://orcid.org/0000-0002-0779-5729Xuelian Tanhttps://orcid.org/0000-0002-6981-7081Abstract 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.http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1678-77572022000100445&lng=en&tlng=enIL-6/STAT3MacrophagePorphyromonas gingivalisApical periodontitisBone lesion |
| spellingShingle | Xuan Chen Jinge Dou Zhuohui Fu Yang Qiu Ling Zou Dingming Huang Xuelian Tan Macrophage M1 polarization mediated via the IL-6/STAT3 pathway contributes to apical periodontitis induced by Porphyromonas gingivalis Journal of Applied Oral Science IL-6/STAT3 Macrophage Porphyromonas gingivalis Apical periodontitis Bone lesion |
| title | 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_short | 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 |
| topic | IL-6/STAT3 Macrophage Porphyromonas gingivalis Apical periodontitis Bone lesion |
| url | http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1678-77572022000100445&lng=en&tlng=en |
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