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Pellino-1 selectively regulates epithelial cell responses to rhinovirus

Research output: Contribution to journalArticlepeer-review

  • Julie A Bennett
  • Lynne R Prince
  • Lisa C Parker
  • Clare A Stokes
  • Harold G de Bruin
  • Maarten van den Berge
  • Irene H Heijink
  • Moira K Whyte
  • Ian Sabroe

Related Edinburgh Organisations

Original languageEnglish
Pages (from-to)6595-604
Number of pages10
JournalJournal of Virology
Volume86
Issue number12
DOIs
Publication statusPublished - Jun 2012

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.

    Research areas

  • Adolescent, Adult, Aged, Cell Line, Cells, Cultured, Epithelial Cells, Female, Humans, Interleukin-1 Receptor-Associated Kinases, Male, Middle Aged, Nuclear Proteins, Picornaviridae Infections, Rhinovirus, Signal Transduction, Toll-Like Receptor 3, Ubiquitin-Protein Ligases, Young Adult

ID: 17208086