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Low-dose ganciclovir ameliorates dextran sulfate sodium-induced ulcerative colitis through inhibiting macrophage STING activation in mice

Ganciclovir (GCV) is a prodrug nucleoside analogue and is clinically used as antiviral drug for the treatment of cytomegalovirus (CMV) and other infections. Based on the potential anti-inflammatory activity of GCV, this study aimed to investigate the therapeutic effects of ganciclovir on dextran sul...

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Autores principales: Gong, Lin-Kong, Yang, Xiaodong, Yang, Juan, Wu, Shu, Chen, Yue, Zhang, Jiang-Tao, Wang, Zhi-Hong, Chen, Li-Hua, Xing, Chungen, Liu, Tong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9714675/
https://www.ncbi.nlm.nih.gov/pubmed/36467059
http://dx.doi.org/10.3389/fphar.2022.1020670
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author Gong, Lin-Kong
Yang, Xiaodong
Yang, Juan
Wu, Shu
Chen, Yue
Zhang, Jiang-Tao
Wang, Zhi-Hong
Chen, Li-Hua
Xing, Chungen
Liu, Tong
author_facet Gong, Lin-Kong
Yang, Xiaodong
Yang, Juan
Wu, Shu
Chen, Yue
Zhang, Jiang-Tao
Wang, Zhi-Hong
Chen, Li-Hua
Xing, Chungen
Liu, Tong
author_sort Gong, Lin-Kong
collection PubMed
description Ganciclovir (GCV) is a prodrug nucleoside analogue and is clinically used as antiviral drug for the treatment of cytomegalovirus (CMV) and other infections. Based on the potential anti-inflammatory activity of GCV, this study aimed to investigate the therapeutic effects of ganciclovir on dextran sulfate sodium (DSS)-induced ulcerative colitis (UC), which may involve cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathways. Our results demonstrated that incubation of GCV (50 μM) inhibited cGAS-STING pathway in macrophage RAW264.7 cells. Then, it was found that intestinal cGAS-STING pathways were upregulated in UC patients, Crohn’s disease colitis (CD) patients, and DSS-induced colitis mice. Intraperitoneal injection of low-dose GCV (10 mg/kg/day) attenuated DSS-induced colitis and abdominal pain in mice. GCV treatment significantly inhibited the upregulation of cGAS-STING pathway in DSS-induced colitis mice. Moreover, DSS-induced colitis and gut dysbiosis was markedly attenuated in STING deficient mice compared with that of wild-type (WT) mice. Finally, there was lacking therapeutic effect of GCV on DSS-induced colitis in STING deficient mice. Together, our results indicated that low-dose GCV ameliorated DSS-induced UC in mice, possibly through inhibiting STING signaling in colonic macrophages, indicating that GCV may be useful for the treatment of UC.
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spelling pubmed-97146752022-12-02 Low-dose ganciclovir ameliorates dextran sulfate sodium-induced ulcerative colitis through inhibiting macrophage STING activation in mice Gong, Lin-Kong Yang, Xiaodong Yang, Juan Wu, Shu Chen, Yue Zhang, Jiang-Tao Wang, Zhi-Hong Chen, Li-Hua Xing, Chungen Liu, Tong Front Pharmacol Pharmacology Ganciclovir (GCV) is a prodrug nucleoside analogue and is clinically used as antiviral drug for the treatment of cytomegalovirus (CMV) and other infections. Based on the potential anti-inflammatory activity of GCV, this study aimed to investigate the therapeutic effects of ganciclovir on dextran sulfate sodium (DSS)-induced ulcerative colitis (UC), which may involve cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathways. Our results demonstrated that incubation of GCV (50 μM) inhibited cGAS-STING pathway in macrophage RAW264.7 cells. Then, it was found that intestinal cGAS-STING pathways were upregulated in UC patients, Crohn’s disease colitis (CD) patients, and DSS-induced colitis mice. Intraperitoneal injection of low-dose GCV (10 mg/kg/day) attenuated DSS-induced colitis and abdominal pain in mice. GCV treatment significantly inhibited the upregulation of cGAS-STING pathway in DSS-induced colitis mice. Moreover, DSS-induced colitis and gut dysbiosis was markedly attenuated in STING deficient mice compared with that of wild-type (WT) mice. Finally, there was lacking therapeutic effect of GCV on DSS-induced colitis in STING deficient mice. Together, our results indicated that low-dose GCV ameliorated DSS-induced UC in mice, possibly through inhibiting STING signaling in colonic macrophages, indicating that GCV may be useful for the treatment of UC. Frontiers Media S.A. 2022-11-17 /pmc/articles/PMC9714675/ /pubmed/36467059 http://dx.doi.org/10.3389/fphar.2022.1020670 Text en Copyright © 2022 Gong, Yang, Yang, Wu, Chen, Zhang, Wang, Chen, Xing and Liu. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pharmacology
Gong, Lin-Kong
Yang, Xiaodong
Yang, Juan
Wu, Shu
Chen, Yue
Zhang, Jiang-Tao
Wang, Zhi-Hong
Chen, Li-Hua
Xing, Chungen
Liu, Tong
Low-dose ganciclovir ameliorates dextran sulfate sodium-induced ulcerative colitis through inhibiting macrophage STING activation in mice
title Low-dose ganciclovir ameliorates dextran sulfate sodium-induced ulcerative colitis through inhibiting macrophage STING activation in mice
title_full Low-dose ganciclovir ameliorates dextran sulfate sodium-induced ulcerative colitis through inhibiting macrophage STING activation in mice
title_fullStr Low-dose ganciclovir ameliorates dextran sulfate sodium-induced ulcerative colitis through inhibiting macrophage STING activation in mice
title_full_unstemmed Low-dose ganciclovir ameliorates dextran sulfate sodium-induced ulcerative colitis through inhibiting macrophage STING activation in mice
title_short Low-dose ganciclovir ameliorates dextran sulfate sodium-induced ulcerative colitis through inhibiting macrophage STING activation in mice
title_sort low-dose ganciclovir ameliorates dextran sulfate sodium-induced ulcerative colitis through inhibiting macrophage sting activation in mice
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9714675/
https://www.ncbi.nlm.nih.gov/pubmed/36467059
http://dx.doi.org/10.3389/fphar.2022.1020670
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