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

被引：4

作者：

Ma, Sai ^{[1
]}

Liu, Anli ^{[1
]}

Hu, Xiang ^{[2
,3
,4
]}

Feng, Qi ^{[1
]}

Zhang, Yanqi ^{[2
]}

Li, Nailin ^{[5
]}

Peng, Jun ^{[1
,6
]}

Sheng, Zi ^{[1
,7
]}

机构：

[1] Shandong Univ, Qilu Hosp, Cheeloo Coll Med, Dept Hematol, Jinan, Peoples R China

[2] Shandong Univ, Qilu Hosp, Cheeloo Coll Med, Shandong Prov Key Lab Immunohematol, Jinan, Peoples R China

[3] Chinese Minist Educ, Lab Cardiovasc Remodeling & Funct Res, Jinan, Peoples R China

[4] Chinese Minist Hlth, Jinan, Peoples R China

[5] Karolinska Inst, Dept Med Solna, Clin Epidemiol Unit, Clin Pharmacol Grp, Stockholm, Sweden

[6] Chinese Acad Med Sci & Peking Union Med Coll, Inst Hematol & Blood Dis Hosp, State Key Lab Expt Hematol, Tianjin, Peoples R China

[7] Shandong Univ, Cheeloo Coll Med, Sch Med, Jinan, Peoples R China

来源：

BIOCHEMICAL PHARMACOLOGY | 2021年 / 186卷

基金：

中国博士后科学基金; 中国国家自然科学基金;

关键词：

Eltrombopag; Thrombocytopenia; Iron chelation; Interferon-; Reactive oxygen species; IFN-stimulated gene; Viral hepatitis; CHRONIC HEPATITIS-B; THROMBOPOIETIN MIMETICS; THROMBOCYTOPENIA; ACTIVATION; MONOCYTES; HOMEOSTASIS; MANAGEMENT; CYTOKINES; CIRRHOSIS; EXPOSURE;

D O I：

10.1016/j.bcp.2021.114436

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

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-? (IFN-?) 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-? through the TPO-Rindependent pathway by mediating reactive oxygen species production by iron chelation. Our results assessed the inhibitory effect of EP on IFN-? 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 hepatitisrelated immunological thrombocytopenia.

引用

页数：8

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