title: IL-10 plays a central regulatory role in the cytokines induced by hepatitis C virus core protein and polyinosinic acid:polycytodylic acid.
abstract: Hepatitis C virus (HCV) can cause persistent infection and chronic liver disease, and viral factors are involved in HCV persistence. HCV core protein, a highly conserved viral protein, not only elicits an immunoresponse, but it also regulates it. In addition, HCV core protein interacts with toll-like receptors (TLRs) on monocytes, inducing them to produce cytokines. Polyinosinic acid:polycytodylic acid (polyI:C) is a synthetic analogue of double-stranded RNA that binds to TLR3 and can induce secretion of type I IFN from monocytes. Cytokine response against HCV is likely to affect the natural course of infection as well as HCV persistence. However, possible effects of cytokines induced by HCV core protein and polyI:C remain to be investigated. In this study, we isolated CD14(+) monocytes from healthy donors, cultured them in the presence of HCV core protein and/or polyI:C, and characterized the induced cytokines, phenotypes and mechanisms. We demonstrated that HCV core protein- and polyI:C-stimulated CD14(+) monocytes secreted tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-10, and type I interferon (IFN). Importantly, TNF-α and IL-1β regulated the secretion of IL-10, which then influenced the expression of signal transducer and activator of transcription 1 (STAT1) and interferon regulatory factor 1 (IRF1) and subsequently the production of type I IFN. Interestingly, type I IFN also regulated the production of IL-10, which in turn inhibited the nuclear factor (NF)-κB subunit, reducing TNF-α and IL-1β levels. Therefore, IL-10 appears to play a central role in regulating the production of cytokines induced by HCV core protein and polyI:C.
authors.affiliation: Department of Hepatology, The First Hospital of Jilin University, Changchun, Jilin 130021, China; Department of Pediatric Gastroenterology, The First Hospital of Jilin University, Changchun, Jilin 130021, China.
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Pang
authors.affiliation: Department of Pediatric Gastroenterology, The First Hospital of Jilin University, Changchun, Jilin 130021, China.
authors.forename: Zhaoxia
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Translational Medicine Research Institute, The First Hospital of Jilin University, Changchun, Jilin 130021, China.
authors.forename: Naicui
authors.initials: N
authors.lastname: Zhai
authors.affiliation: Department of Hepatology, The First Hospital of Jilin University, Changchun, Jilin 130021, China.
authors.forename: Qianqian
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Translational Medicine Research Institute, The First Hospital of Jilin University, Changchun, Jilin 130021, China.
authors.forename: Hongxiao
authors.initials: H
authors.lastname: Song
authors.affiliation: Department of Hepatology, The First Hospital of Jilin University, Changchun, Jilin 130021, China.
authors.forename: Yujiao
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Translational Medicine Research Institute, The First Hospital of Jilin University, Changchun, Jilin 130021, China.
authors.forename: Tianyang
authors.initials: T
authors.lastname: Li
authors.affiliation: Translational Medicine Research Institute, The First Hospital of Jilin University, Changchun, Jilin 130021, China.
authors.forename: Haijun
authors.initials: H
authors.lastname: Li
authors.affiliation: Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill, Chapel Hill, NC, United States; Department of Microbiology and Immunology, The University of North Carolina at Chapel Hill, Chapel Hill, NC, United States.
authors.forename: Lishan
authors.initials: L
authors.lastname: Su
authors.affiliation: Department of Hepatology, The First Hospital of Jilin University, Changchun, Jilin 130021, China. Electronic address: junqiniu2013@126.com.
authors.forename: Junqi
authors.initials: J
authors.lastname: Niu
authors.affiliation: Translational Medicine Research Institute, The First Hospital of Jilin University, Changchun, Jilin 130021, China. Electronic address: zhengkuntu2013@126.com.
authors.forename: Zhengkun
authors.initials: Z
authors.lastname: Tu
mesh_terms: D000328:Adult; D002478:Cells, Cultured; D005260:Female; D016174:Hepacivirus / Q000276:immunology*; D019698:Hepatitis C, Chronic / Q000276:immunology*; D006801:Humans; D050856:Interferon Regulatory Factor-1 / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism*; D018950:Lipopolysaccharide Receptors / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology* / Q000821:virology; D016328:NF-kappa B / Q000378:metabolism; D011070:Poly I-C / Q000378:metabolism*; D050794:STAT1 Transcription Factor / Q000378:metabolism; D051196:Toll-Like Receptor 3 / Q000378:metabolism; D014758:Viral Core Proteins / Q000378:metabolism*; D055815:Young Adult
chemical_list: C494257:IRF1 protein, human; D050856:Interferon Regulatory Factor-1; D018950:Lipopolysaccharide Receptors; D016328:NF-kappa B; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; C495344:TLR3 protein, human; D051196:Toll-Like Receptor 3; D014758:Viral Core Proteins; C069130:nucleocapsid protein, Hepatitis C virus; D016753:Interleukin-10; D011070:Poly I-C
keywords: A central role; Antiviral cytokines; IL-10; Inflammatory cytokines; Negative feedback