Halofuginone alleviates acute viral myocarditis in suckling BALB/c mice by inhibiting TGF-β1
- Department of Emergency, Xi’an Children’s Hospital, Xi'an, 710003, Shanxi (China)
- Department of Infection, Xi’an Children’s Hospital, Xi'an, 710003, Shanxi (China)
- Department of Respiration, Xi’an Children’s Hospital, NO. 69 Xijuyuan Lane, Xi'an 710003, Shanxi (China)
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. - Highlights: • Halofuginone (HF) increases the survival of suckling BALB/c mice infected with acute CVB3. • HF reduces the expression of Th17 cell markers (IL-17 and IL-23) and the number of CD4{sup +} IL17{sup +} cells. • Pro-inflammatory cytokines levels associated with myocarditis were reduced by HF in CVB3-treated suckling mice. • HF alleviates VMC via inhibition of TGF-β1-mediated NF-κB p65/TNF-α pathway.
- OSTI ID:
- 22596365
- Journal Information:
- Biochemical and Biophysical Research Communications, Journal Name: Biochemical and Biophysical Research Communications Journal Issue: 2 Vol. 473; ISSN 0006-291X; ISSN BBRCA9
- Country of Publication:
- United States
- Language:
- English
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