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FTY720 alleviates coxsackievirus B3‐induced myocarditis and inhibits viral replication through regulating sphingosine 1‐phosphate receptors and AKT/caspase‐3 pathways
Author(s) -
Wang Xinggang,
Li Minghui,
Yu Ying,
Liu Guijian,
Yu Yong,
Zou Yunzeng,
Ge Junbo,
Chen Ruizhen
Publication year - 2019
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.28434
Subject(s) - protein kinase b , sphingosine 1 phosphate receptor , apoptosis , sphingosine 1 phosphate , viral replication , microbiology and biotechnology , sphingosine , sphingosine kinase , s1pr1 , biology , pi3k/akt/mtor pathway , caspase 3 , caspase , signal transduction , receptor , cancer research , immunology , virus , programmed cell death , biochemistry , vascular endothelial growth factor a , vegf receptors , vascular endothelial growth factor
Fingolimod (FTY720) after phosphorylation, as the ligand of sphingosine 1‐phosphate receptors (S1PRs), plays an important role in cell proliferation and differentiation. In this article, FTY720 in the treatment of coxsackievirus B3 (CVB3)‐induced viral myocarditis was closely related to apoptosis and AKT/caspase‐3 apoptotic pathways. We found that CVB3 inhibited myocardial apoptosis at the early stage with upregulating p‐AKT level and downregulating activated caspase‐3 level for replication of virus progeny, whereas it promoted apoptosis at a late stage with downregulating p‐AKT and upregulating activated caspase‐3 for releasing the newly synthesized virus to spread. Interestingly, FTY720 could reverse this trend; it promoted apoptosis at an early stage and inhibited apoptosis at the late stage in vivo and vitro, which proved the antiviral effect. We also found that S1PR1, S1PR4, and S1PR5, rather than S1PR2 and S1PR3, were regulated by FTY720 in this process. The results confirmed that FTY720 alleviates CVB3‐induced myocarditis and inhibits viral replication through regulating S1PRs and AKT/caspase‐3 pathways with a bidirectional regulation of apoptosis.