Neutralization of interleukin-38 exacerbates coxsackievirus B3-induced acute myocarditis in mice

Abstract Background Interleukin (IL)-38, a novel member of the IL-1 family, has been reported to be involved in several diseases associated with viral infection. However, the expression and functional role of IL-38 in acute viral myocarditis (AVMC) have not been investigated. Methods Male BALB/c mic...

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Autores principales:	Yimin Xue, Mingguang Chen, Qian Chen, Tingfeng Huang, Qiaolian Fan, Fenghui Lin, Jun Ke, Feng Chen
Formato:	article
Lenguaje:	EN
Publicado:	BMC 2021
Materias:	Acute viral myocarditis IL-38 Th1 cells Th17 cells Coxsackievirus B3 Infectious and parasitic diseases RC109-216
Acceso en línea:	https://doaj.org/article/15dcb6d8fbf7414eb422f00160aa07af
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spelling	oai:doaj.org-article:15dcb6d8fbf7414eb422f00160aa07af2021-11-21T12:02:11ZNeutralization of interleukin-38 exacerbates coxsackievirus B3-induced acute myocarditis in mice10.1186/s12985-021-01687-w1743-422Xhttps://doaj.org/article/15dcb6d8fbf7414eb422f00160aa07af2021-11-01T00:00:00Zhttps://doi.org/10.1186/s12985-021-01687-whttps://doaj.org/toc/1743-422XAbstract Background Interleukin (IL)-38, a novel member of the IL-1 family, has been reported to be involved in several diseases associated with viral infection. However, the expression and functional role of IL-38 in acute viral myocarditis (AVMC) have not been investigated. Methods Male BALB/c mice were treated with intraperitoneal (i.p.) injection of coxsackievirus B3 (CVB3) for establishing AVMC models. On day 7 post-injection, the expression of IL-38 and IL-36R (IL-36 receptor) were measured. Mice were then treated with i.p. injection of mouse Anti-IL-38 Antibodies (Abs) for neutralization of IL-38. The survival, bodyweight loss, cardiac function, and myocarditis severity of mice were recorded. The percentages of splenic Th1 and Th17 cells, the expression levels of Th1/Th17-related master transcription factors (T-bet and RORγt) and cytokines were determined by flow cytometry, RT-qPCR, and ELISA, respectively. Cardiac viral replication was further detected. Results The mRNA and protein expression levels of IL-38 in myocardium and serum, as well as cardiac IL-36R mRNA levels were significantly elevated in mice with AVMC. Increased IL-38 levels were negatively correlated with the severity of AVMC. Neutralization of IL-38 exacerbated CVB3-induced AVMC, as verified by the lower survival rate, impaired cardiac function, continuous bodyweight loss, and higher values of HW/BW and cardiac pathological scores. In addition, neutralization of IL-38 suppressed Th1 cells differentiation while promoted Th17 cells differentiation, accompanied by decreased T-bet mRNA expression and increased RORγt expression. Down-regulation of IFN-γ and up-regulation of IL-17, TNF-α, and IL-6 mRNA and protein expression levels in myocardium and serum were also observed in the IL-38 neutralization group. Furthermore, neutralization of IL-38 markedly promoted cardiac viral replication. Conclusions Neutralization of IL-38 exacerbates CVB3-induced AVMC in mice, which may be attributable to the imbalance of Th1/Th17 cells and increased CVB3 replication. Thus, IL-38 can be considered as a potential therapeutic target for AVMC.Yimin XueMingguang ChenQian ChenTingfeng HuangQiaolian FanFenghui LinJun KeFeng ChenBMCarticleAcute viral myocarditisIL-38Th1 cellsTh17 cellsCoxsackievirus B3Infectious and parasitic diseasesRC109-216ENVirology Journal, Vol 18, Iss 1, Pp 1-13 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Acute viral myocarditis IL-38 Th1 cells Th17 cells Coxsackievirus B3 Infectious and parasitic diseases RC109-216
spellingShingle	Acute viral myocarditis IL-38 Th1 cells Th17 cells Coxsackievirus B3 Infectious and parasitic diseases RC109-216 Yimin Xue Mingguang Chen Qian Chen Tingfeng Huang Qiaolian Fan Fenghui Lin Jun Ke Feng Chen Neutralization of interleukin-38 exacerbates coxsackievirus B3-induced acute myocarditis in mice
description	Abstract Background Interleukin (IL)-38, a novel member of the IL-1 family, has been reported to be involved in several diseases associated with viral infection. However, the expression and functional role of IL-38 in acute viral myocarditis (AVMC) have not been investigated. Methods Male BALB/c mice were treated with intraperitoneal (i.p.) injection of coxsackievirus B3 (CVB3) for establishing AVMC models. On day 7 post-injection, the expression of IL-38 and IL-36R (IL-36 receptor) were measured. Mice were then treated with i.p. injection of mouse Anti-IL-38 Antibodies (Abs) for neutralization of IL-38. The survival, bodyweight loss, cardiac function, and myocarditis severity of mice were recorded. The percentages of splenic Th1 and Th17 cells, the expression levels of Th1/Th17-related master transcription factors (T-bet and RORγt) and cytokines were determined by flow cytometry, RT-qPCR, and ELISA, respectively. Cardiac viral replication was further detected. Results The mRNA and protein expression levels of IL-38 in myocardium and serum, as well as cardiac IL-36R mRNA levels were significantly elevated in mice with AVMC. Increased IL-38 levels were negatively correlated with the severity of AVMC. Neutralization of IL-38 exacerbated CVB3-induced AVMC, as verified by the lower survival rate, impaired cardiac function, continuous bodyweight loss, and higher values of HW/BW and cardiac pathological scores. In addition, neutralization of IL-38 suppressed Th1 cells differentiation while promoted Th17 cells differentiation, accompanied by decreased T-bet mRNA expression and increased RORγt expression. Down-regulation of IFN-γ and up-regulation of IL-17, TNF-α, and IL-6 mRNA and protein expression levels in myocardium and serum were also observed in the IL-38 neutralization group. Furthermore, neutralization of IL-38 markedly promoted cardiac viral replication. Conclusions Neutralization of IL-38 exacerbates CVB3-induced AVMC in mice, which may be attributable to the imbalance of Th1/Th17 cells and increased CVB3 replication. Thus, IL-38 can be considered as a potential therapeutic target for AVMC.
format	article
author	Yimin Xue Mingguang Chen Qian Chen Tingfeng Huang Qiaolian Fan Fenghui Lin Jun Ke Feng Chen
author_facet	Yimin Xue Mingguang Chen Qian Chen Tingfeng Huang Qiaolian Fan Fenghui Lin Jun Ke Feng Chen
author_sort	Yimin Xue
title	Neutralization of interleukin-38 exacerbates coxsackievirus B3-induced acute myocarditis in mice
title_short	Neutralization of interleukin-38 exacerbates coxsackievirus B3-induced acute myocarditis in mice
title_full	Neutralization of interleukin-38 exacerbates coxsackievirus B3-induced acute myocarditis in mice
title_fullStr	Neutralization of interleukin-38 exacerbates coxsackievirus B3-induced acute myocarditis in mice
title_full_unstemmed	Neutralization of interleukin-38 exacerbates coxsackievirus B3-induced acute myocarditis in mice
title_sort	neutralization of interleukin-38 exacerbates coxsackievirus b3-induced acute myocarditis in mice
publisher	BMC
publishDate	2021
url	https://doaj.org/article/15dcb6d8fbf7414eb422f00160aa07af
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Neutralization of interleukin-38 exacerbates coxsackievirus B3-induced acute myocarditis in mice

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