title: Halofuginone alleviates acute viral myocarditis in suckling BALB/c mice by inhibiting TGF-β1.
abstract: Viral myocarditis (VMC) is an inflammation of heart muscle in infants and young adolescents. This study explored the function of halofuginone (HF) in Coxsackievirus B3 (CVB3) -treated suckling mice. HF-treated animal exhibited higher survival rate, lower heart/body weight, and more decreased blood sugar concentration than CVB3 group. HF also reduced the expressions of interleukin(IL)-17 and IL-23 and the numbers of Th17 cells. Moreover, HF downregulated pro-inflammatory cytokine levels and increased anti-inflammatory cytokine levels. The expressions of transforming growth factor(TGF-β1) and nuclear factor kappa-light-chain-enhancer of activated B (NF-κB) p65/ tumor necrosis factor-α (TNF-α) proteins were decreased by HF as well. Finally, the overexpression of TGF-β1 counteracted the protection effect of HF in CVB3-treated suckling mice. In summary, our study suggests HF increases the survival of CVB3 suckling mice, reduces the Th17 cells and pro-inflammatory cytokine levels, and may through downregulation of the TGF-β1-mediated expression of NF-κB p65/TNF-α pathway proteins. These results offer a potential therapeutic strategy for the treatment of VMC.
authors.affiliation: Department of Emergency, Xi'an Children's Hospital, Xi'an, 710003, Shanxi, PR China.
authors.forename: Xiao-Hua
authors.initials: XH
authors.lastname: Sun
authors.affiliation: Department of Infection, Xi'an Children's Hospital, Xi'an, 710003, Shanxi, PR China.
authors.forename: Jia
authors.initials: J
authors.lastname: Fu
authors.affiliation: Department of Respiration, Xi'an Children's Hospital, NO. 69 Xijuyuan Lane, Xi'an 710003, Shanxi, PR China. Electronic address: daqingsuncd@163.com.
authors.forename: Da-Qing
authors.initials: DQ
authors.lastname: Sun
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D003384:Coxsackievirus Infections / Q000150:complications* / Q000188:drug therapy / Q000276:immunology; D029822:Enterovirus B, Human / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009205:Myocarditis / Q000188:drug therapy* / Q000276:immunology / Q000821:virology*; D016328:NF-kappa B / Q000276:immunology; D010880:Piperidines / Q000627:therapeutic use*; D052999:Quinazolinones / Q000627:therapeutic use*; D015398:Signal Transduction / Q000187:drug effects; D058504:Th17 Cells / Q000187:drug effects / Q000276:immunology / Q000821:virology; D053773:Transforming Growth Factor beta1 / Q000037:antagonists & inhibitors* / Q000276:immunology
chemical_list: D000893:Anti-Inflammatory Agents; D016328:NF-kappa B; D010880:Piperidines; D052999:Quinazolinones; D053773:Transforming Growth Factor beta1; C010176:halofuginone
keywords: Halofuginone; Inflammatory cytokines; TGF-β1; Th17 cells; Viral myocarditis