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Rotavirus infects human biliary epithelial cells and stimulates secretion of cytokines IL-6 and IL-8 via MAPK pathway

Clemente, Maria Grazia and Patton, John T. and Anders, Robert Albert and Yolken, Robert H. and Schwarz, Kathleen (2015) Rotavirus infects human biliary epithelial cells and stimulates secretion of cytokines IL-6 and IL-8 via MAPK pathway. BioMed Research International, Vol. 2015 , Article 697238. ISSN 2314-6133. eISSN 2314-6141. Article.

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DOI: 10.1155/2015/697238

Abstract

Biliary atresia (BA) is an infantile inflammatory cholangiopathy of unknown etiology although epidemiologic studies and animal models utilizing rotavirus (RV) have suggested a role for viral infection. Proinflammatory and profibrotic cytokines have been detected in infants with BA.The purpose of our study was to investigate the susceptibility of human cholangiocytes (H69 cells) to infection with RRV and to determine if this infection resulted in cytokine secretion. Infection ofH69 cells by RRV was noncytolytic and resulted in a time-dependent increase in the release of both infectious virions and cytokines IL-6 and IL-8 into the supernate. The greatest difference in cytokine supernatant levels between infected and mock-infected cells was noted at 24 hours postinfection (h p.i.) for IL-8, 556 ± 111 versus 77 ± 68 pg/mL (𝑝 < 0.0001), and at 48 h p.i. for IL-6, 459 ± 64 versus 67 ± 2 pg/mL (𝑝 < 0.0001). Production of both cytokines following RRV infection was significantly reduced by pretreating the H69 cells with inhibitors of mitogen-activated protein kinase (MAPK). Conclusion. RRV can infect human cholangiocytes resulting in the production of proinflammatory and profibrotic cytokines via the MAPK pathway. RRV-infected H69 cells could be a useful model system for investigating the viral hypothesis of BA.

Item Type:Article
ID Code:11245
Status:Published
Refereed:Yes
Uncontrolled Keywords:Biliary atresia, pediatric liver disease, hepatic fibrosis
Subjects:Area 06 - Scienze mediche > MED/38 Pediatria generale e specialistica
Divisions:001 Università di Sassari > 01-a Nuovi Dipartimenti dal 2012 > Scienze Chirurgiche, Microchirurgiche e Mediche
Publisher:Hindawi Publishing Corporation
ISSN:2314-6133
eISSN:2314-6141
Copyright Holders:© 2015 Maria Grazia Clemente et al.
Deposited On:13 Jan 2016 12:13

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