Inhibition of the CXCL9-CXCR3 axis suppresses the progression of experimental apical periodontitis by blocking macrophage migration and activation

Abstract Apical periodontitis (AP) is an acute or chronic inflammatory disease caused by complex interactions between infected root canal and host immune system. It results in the induction of inflammatory mediators such as chemokines and cytokines leading to periapical tissue destruction. To unders...

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Autores principales:	Tatsuya Hasegawa, V. Venkata Suresh, Yoshio Yahata, Masato Nakano, Shigeto Suzuki, Shigeki Suzuki, Satoru Yamada, Hideki Kitaura, Itaru Mizoguchi, Yuichiro Noiri, Keisuke Handa, Masahiro Saito
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/610192dc9c4643eab26692061c014b01
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spelling	oai:doaj.org-article:610192dc9c4643eab26692061c014b012021-12-02T13:57:25ZInhibition of the CXCL9-CXCR3 axis suppresses the progression of experimental apical periodontitis by blocking macrophage migration and activation10.1038/s41598-021-82167-72045-2322https://doaj.org/article/610192dc9c4643eab26692061c014b012021-01-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-82167-7https://doaj.org/toc/2045-2322Abstract Apical periodontitis (AP) is an acute or chronic inflammatory disease caused by complex interactions between infected root canal and host immune system. It results in the induction of inflammatory mediators such as chemokines and cytokines leading to periapical tissue destruction. To understand the molecular pathogenesis of AP, we have investigated inflammatory-related genes that regulate AP development. We found here that macrophage-derived CXCL9, which acts through CXCR3, is recruited by progressed AP. The inhibition of CXCL9 by a CXCR3 antagonist reduced the lesion size in a mouse AP model with decreasing IL-1β, IL-6 and TNFα expression. The treatment of peritoneal macrophages with CXCL9 and LPS induced the transmigration and upregulation of osteoclastogenic cytokines such as IL-1β, IL-6 and matrix metalloprotease 2, a marker of activated macrophages. This suggests that the CXCL9-CXCR3 axis plays a crucial role in the development of AP, mediated by the migration and activation of macrophages for periapical tissue destruction. Our data thus show that CXCL9 regulates the functions of macrophages which contribute to AP pathogenesis, and that blocking CXCL9 suppresses AP progression. Knowledge of the principal factors involved in the progression of AP, and the identification of related inflammatory markers, may help to establish new therapeutic strategies.Tatsuya HasegawaV. Venkata SureshYoshio YahataMasato NakanoShigeto SuzukiShigeki SuzukiSatoru YamadaHideki KitauraItaru MizoguchiYuichiro NoiriKeisuke HandaMasahiro SaitoNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-15 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Tatsuya Hasegawa V. Venkata Suresh Yoshio Yahata Masato Nakano Shigeto Suzuki Shigeki Suzuki Satoru Yamada Hideki Kitaura Itaru Mizoguchi Yuichiro Noiri Keisuke Handa Masahiro Saito Inhibition of the CXCL9-CXCR3 axis suppresses the progression of experimental apical periodontitis by blocking macrophage migration and activation
description	Abstract Apical periodontitis (AP) is an acute or chronic inflammatory disease caused by complex interactions between infected root canal and host immune system. It results in the induction of inflammatory mediators such as chemokines and cytokines leading to periapical tissue destruction. To understand the molecular pathogenesis of AP, we have investigated inflammatory-related genes that regulate AP development. We found here that macrophage-derived CXCL9, which acts through CXCR3, is recruited by progressed AP. The inhibition of CXCL9 by a CXCR3 antagonist reduced the lesion size in a mouse AP model with decreasing IL-1β, IL-6 and TNFα expression. The treatment of peritoneal macrophages with CXCL9 and LPS induced the transmigration and upregulation of osteoclastogenic cytokines such as IL-1β, IL-6 and matrix metalloprotease 2, a marker of activated macrophages. This suggests that the CXCL9-CXCR3 axis plays a crucial role in the development of AP, mediated by the migration and activation of macrophages for periapical tissue destruction. Our data thus show that CXCL9 regulates the functions of macrophages which contribute to AP pathogenesis, and that blocking CXCL9 suppresses AP progression. Knowledge of the principal factors involved in the progression of AP, and the identification of related inflammatory markers, may help to establish new therapeutic strategies.
format	article
author	Tatsuya Hasegawa V. Venkata Suresh Yoshio Yahata Masato Nakano Shigeto Suzuki Shigeki Suzuki Satoru Yamada Hideki Kitaura Itaru Mizoguchi Yuichiro Noiri Keisuke Handa Masahiro Saito
author_facet	Tatsuya Hasegawa V. Venkata Suresh Yoshio Yahata Masato Nakano Shigeto Suzuki Shigeki Suzuki Satoru Yamada Hideki Kitaura Itaru Mizoguchi Yuichiro Noiri Keisuke Handa Masahiro Saito
author_sort	Tatsuya Hasegawa
title	Inhibition of the CXCL9-CXCR3 axis suppresses the progression of experimental apical periodontitis by blocking macrophage migration and activation
title_short	Inhibition of the CXCL9-CXCR3 axis suppresses the progression of experimental apical periodontitis by blocking macrophage migration and activation
title_full	Inhibition of the CXCL9-CXCR3 axis suppresses the progression of experimental apical periodontitis by blocking macrophage migration and activation
title_fullStr	Inhibition of the CXCL9-CXCR3 axis suppresses the progression of experimental apical periodontitis by blocking macrophage migration and activation
title_full_unstemmed	Inhibition of the CXCL9-CXCR3 axis suppresses the progression of experimental apical periodontitis by blocking macrophage migration and activation
title_sort	inhibition of the cxcl9-cxcr3 axis suppresses the progression of experimental apical periodontitis by blocking macrophage migration and activation
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/610192dc9c4643eab26692061c014b01
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Inhibition of the CXCL9-CXCR3 axis suppresses the progression of experimental apical periodontitis by blocking macrophage migration and activation

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