title: Ribavirin enhances myeloid-derived suppressor cell differentiation through CXCL9/10 downregulation.
abstract: Elevation of myeloid-derived suppressor cells (MDSCs) was observed in some viral infectious diseases. In this study, we studied whether ribavirin, a widely used clinical antiviral drug, could impact the differentiation of human MDSCs in vitro. Flow cytometric analysis showed that ribavirin treatment (5-20 µg/ml) significantly enhanced the differentiation of monocytic MDSCs in a dose-dependent manner. The ribavirin-generated MDSCs were immune-suppressive toward autologous T cells. The mRNA expression of some cytokines was further examined by quantitative reverse transcription polymerase chain reaction. We observed a significant down-regulation of chemokine (C-X-C motif) ligand 9 (CXCL9) and CXCL10 mRNA in ribavirin-generated MDSCs, when compared with control. Peripheral blood mononuclear cells from clinical chronic hepatitis C patients subjected to ribavirin therapy also displayed a similar suppression in CXCL9/10 mRNA expression. Administration of recombinant CXCL9/10 proteins clearly counteracted the effect of ribavirin on MDSCs. In summary, this study showed that ribavirin enhanced human MDSCs differentiation in vitro, which may be attribute to the down-regulation of CXCL9/10 expression.
authors.affiliation: School of Medicine, Zhejiang University City College , Hangzhou, Zhejiang , PR China .
authors.forename: Jingyin
authors.initials: J
authors.lastname: Dong
authors.forename: Jianyang
authors.initials: J
authors.lastname: Wei
authors.forename: Limei
authors.initials: L
authors.lastname: Zhong
authors.forename: Qiong
authors.initials: Q
authors.lastname: Yang
authors.forename: Jiuling
authors.initials: J
authors.lastname: Tuo
authors.forename: Pan
authors.initials: P
authors.lastname: Zhou
authors.forename: Jie
authors.initials: J
authors.lastname: Fang
authors.forename: Weiping
authors.initials: W
authors.lastname: Cai
authors.forename: Xiaoyi
authors.initials: X
authors.lastname: Sun
authors.forename: Jie
authors.initials: J
authors.lastname: Zhou
mesh_terms: D000998:Antiviral Agents / Q000494:pharmacology*; D018929:Cell Culture Techniques; D002454:Cell Differentiation / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D054357:Chemokine CXCL10 / Q000096:biosynthesis*; D054370:Chemokine CXCL9 / Q000096:biosynthesis*; D015536:Down-Regulation; D005434:Flow Cytometry; D006801:Humans; D022423:Myeloid Cells / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D012254:Ribavirin / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology
chemical_list: D000998:Antiviral Agents; C114753:CXCL10 protein, human; C080810:CXCL9 protein, human; D054357:Chemokine CXCL10; D054370:Chemokine CXCL9; D012254:Ribavirin
keywords: Chemokine (C-X-C motif) ligand; myeloid-derived suppressor cells; ribavirin