title: Pellino-1 selectively regulates epithelial cell responses to rhinovirus.
abstract: Pellino-1 has recently been identified as a regulator of interleukin-1 (IL-1) signaling, but its roles in regulation of responses of human cells to human pathogens are unknown. We investigated the potential roles of Pellino-1 in the airways. We show for the first time that Pellino-1 regulates responses to a human pathogen, rhinovirus minor group serotype 1B (RV-1B). Knockdown of Pellino-1 by small interfering RNA (siRNA) was associated with impaired production of innate immune cytokines such as CXCL8 from human primary bronchial epithelial cells in response to RV-1B, without impairment in production of antiviral interferons (IFN), and without loss of control of viral replication. Pellino-1 actions were likely to be independent of interleukin-1 receptor-associated kinase-1 (IRAK-1) regulation, since Pellino-1 knockdown in primary epithelial cells did not alter responses to IL-1 but did inhibit responses to poly(I·C), a Toll-like receptor 3 (TLR3) activator that does not signal via IRAK-1 to engender a response. These data indicate that Pellino-1 represents a novel target that regulates responses of human airways to human viral pathogens, independently of IRAK signaling. Neutralization of Pellino-1 may therefore provide opportunities to inhibit potentially harmful neutrophilic inflammation of the airways induced by respiratory viruses, without loss of control of the underlying viral infection.
authors.affiliation: Academic Unit of Respiratory Medicine, Department of Infection and Immunity, Faculty of Medicine, Dentistry and Health, University of Sheffield, Sheffield, United Kingdom.
authors.forename: Julie A
authors.initials: JA
authors.lastname: Bennett
authors.forename: Lynne R
authors.initials: LR
authors.lastname: Prince
authors.forename: Lisa C
authors.initials: LC
authors.lastname: Parker
authors.forename: Clare A
authors.initials: CA
authors.lastname: Stokes
authors.forename: Harold G
authors.initials: HG
authors.lastname: de Bruin
authors.forename: Maarten
authors.initials: M
authors.lastname: van den Berge
authors.forename: Irene H
authors.initials: IH
authors.lastname: Heijink
authors.forename: Moira K
authors.initials: MK
authors.lastname: Whyte
authors.forename: Ian
authors.initials: I
authors.lastname: Sabroe
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002460:Cell Line; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000276:immunology* / Q000821:virology; D005260:Female; D006801:Humans; D053592:Interleukin-1 Receptor-Associated Kinases / Q000235:genetics / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins / Q000235:genetics / Q000276:immunology*; D010850:Picornaviridae Infections / Q000235:genetics / Q000276:immunology* / Q000821:virology; D012229:Rhinovirus / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D015398:Signal Transduction; D051196:Toll-Like Receptor 3 / Q000235:genetics / Q000276:immunology; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000276:immunology*; D055815:Young Adult
chemical_list: D009687:Nuclear Proteins; D051196:Toll-Like Receptor 3; C485959:PELI1 protein, human; D044767:Ubiquitin-Protein Ligases; D053592:Interleukin-1 Receptor-Associated Kinases