title: Enterovirus infection induces cytokine and chemokine expression in insulin-producing cells.
abstract: Despite evidence supporting an association between enterovirus (EV) infection and type 1 diabetes, the etiological mechanism(s) for EV-induced beta cell destruction is(are) not well understood. In this study, the effects of Coxsackievirus B (CVB) 1-6 on cell lysis and cytokine/chemokine expression in the insulinoma-1 (INS-1) beta cell line were investigated. Cytolysis was assessed using tissue culture infectious dose 50 (TCID(50)). Quantitative RT-PCR was used to measure viral RNA and mRNA of cytokines interferon (IFN)-α, IFN-β, IFN-γ, tumor necrosis factor (TNF)-α, and chemokine (C-X-C motif) ligand 10 (CXCL10), chemokine (C-C motif) ligand 2 (CCL2), and chemokine (C-C motif) ligand 5 (CCL5) in infected INS-1 cells. CVB2, 4, 5, and 6 lysed and replicated in INS-1 cells; TCID(50) was lowest for CVB5 and highest for CVB6. IFN-γ, CXCL10, and CCL5 mRNA levels all increased significantly following infection with CVB2, 4, 5, and 6 (P<0.05). CCL2 mRNA increased with CVB2, 5, and 6 (P<0.05), IFN-α mRNA increased with CVB5 infection (P<0.05), while TNF-α mRNA and IFN-β mRNA (P<0.001) increased with CVB2 infection. Dose-dependent effects of infection on cytokine mRNA levels were observed for all (P<0.01) except IFN-γ. Following inoculation of INS-1 cells with CVB1 and 3, viral RNA was not detected and cytokine/chemokine mRNA levels were unchanged. In conclusion, CVB2, 4, 5, and 6 induce dose-dependent cytokine and chemokine mRNA production from INS-1 cells suggesting that pro-inflammatory cytokine and chemokine secretion by beta cells is a potential mechanism for EV-induced beta cell damage in type 1 diabetes.
authors.affiliation: Virology Research, POWH and UNSW Research Laboratories, South Eastern Area Laboratory Services, Prince of Wales Hospital, Sydney, NSW, Australia.
authors.forename: Sandhya
authors.initials: S
authors.lastname: Nair
authors.forename: Kin-Chuen
authors.initials: KC
authors.lastname: Leung
authors.forename: William D
authors.initials: WD
authors.lastname: Rawlinson
authors.forename: Zin
authors.initials: Z
authors.lastname: Naing
authors.forename: Maria E
authors.initials: ME
authors.lastname: Craig
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D054357:Chemokine CXCL10 / Q000378:metabolism; D018925:Chemokines / Q000378:metabolism*; D019742:Chemokines, CC / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism*; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology / Q000821:virology; D029822:Enterovirus B, Human / Q000276:immunology* / Q000472:pathogenicity*; D006801:Humans; D007249:Inflammation / Q000276:immunology* / Q000378:metabolism; D050417:Insulin-Secreting Cells / Q000276:immunology* / Q000378:metabolism* / Q000821:virology; D007340:Insulinoma / Q000276:immunology / Q000378:metabolism / Q000821:virology; D007372:Interferons / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D054357:Chemokine CXCL10; D018925:Chemokines; D019742:Chemokines, CC; D016207:Cytokines; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D007372:Interferons