Eltrombopag inhibits Type I interferon-mediated antiviral signaling by decreasing cellular iron

艾曲波帕通过降低细胞铁来抑制 I 型干扰素介导的抗病毒信号传导

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作者:Sai Ma, Anli Liu, Xiang Hu, Qi Feng, Yanqi Zhang, Nailin Li, Jun Peng, Zi Sheng

Abstract

Thrombocytopenia is common among patients with viral hepatitis, limiting the use of antiviral therapy. Eltrombopag (EP) is a thrombopoietin receptor (TPO-R) agonist that has been approved for treatment of immune thrombocytopenia patients with hepatitis virus infection. Interferon-α (IFN-α) plays a crucial role in the antiviral response, and is recommended as the first-line agent for chronic hepatitis B patients. Here, we investigated whether EP inhibits the production of IFN-stimulated genes (ISGs) induced by IFN-α through the TPO-R-independent pathway by mediating reactive oxygen species production by iron chelation. Our results assessed the inhibitory effect of EP on IFN-α signaling, which contributes to the downregulation of ISGs produced by monocytes and sheds light on the underlying mechanisms using iron chelation to treat patients with hepatitis-related immunological thrombocytopenia.

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