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- Title
Enterovirus infection induces cytokine and chemokine expression in insulin-producing cells.
- Authors
Nair, Sandhya; Leung, Kin-Chuen; Rawlinson, William D.; Naing, Zin; Craig, Maria E.
- 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 (TCID50). 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; TCID50 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. J. Med. Virol. 82:1950-1957, 2010. © 2010 Wiley-Liss, Inc.
- Publication
Journal of Medical Virology, 2010, Vol 82, Issue 11, p1950
- ISSN
0146-6615
- Publication type
Article
- DOI
10.1002/jmv.21900