title: Rotavirus Infects Human Biliary Epithelial Cells and Stimulates Secretion of Cytokines IL-6 and IL-8 via MAPK Pathway.
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 of H69 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.
authors.affiliation: Pediatric Liver Center, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA ; Pediatric Clinic, Department of Surgery, Microsurgery and Medical Sciences, University of Sassari, 07100 Sassari, Italy.
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Clemente
authors.affiliation: Virginia-Maryland Regional College of Veterinary Medicine, University of Maryland, College Park, MD 20742, USA.
authors.forename: John T
authors.initials: JT
authors.lastname: Patton
authors.affiliation: Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Anders
authors.affiliation: The Stanley Division of Developmental Neurovirology, Johns Hopkins School of Medicine, Baltimore, MD 21287, USA.
authors.forename: Robert H
authors.initials: RH
authors.lastname: Yolken
authors.affiliation: Pediatric Liver Center, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
authors.forename: Kathleen B
authors.initials: KB
authors.lastname: Schwarz
mesh_terms: D001652:Bile Ducts / Q000276:immunology* / Q000821:virology*; D002460:Cell Line; D006801:Humans; D015850:Interleukin-6 / Q000276:immunology*; D016209:Interleukin-8 / Q000276:immunology*; D020935:MAP Kinase Signaling System / Q000276:immunology*; D012401:Rotavirus / Q000502:physiology*; D015854:Up-Regulation / Q000276:immunology
chemical_list: C508600:IL6 protein, human; D015850:Interleukin-6; D016209:Interleukin-8