Pellino-1 Selectively Regulates Epithelial Cell Responses to Rhinovirus

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*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

19 Citations (Scopus)

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 center dot 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.

Original languageEnglish
Pages (from-to)6595-6604
Number of pages10
JournalJournal of Virology
Volume86
Issue number12
DOIs
Publication statusPublished - Jun-2012

Keywords

  • 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
  • Journal Article
  • Research Support, Non-U.S. Gov't

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