Rhinovirus stimulation of lnterleukin-6 in vivo and in vitro: Evidence for nuclear factor κB-dependent transcriptional activation

Zhou Zhu, Weiliang Tang, Anuradha Ray, Yang Wu, Oskar Einarsson, Marie L. Landry, Jack Gwaltney, Jack A. Elias

Research output: Contribution to journalArticle

Abstract

To further understand the biology of rhinovirus (RV), we determined whether IL-6 was produced during RV infections and characterized the mechanism by which RV stimulates lung cell IL-6 production. In contrast to normals and minimally symptomatic volunteers, IL-6 was detected in the nasal washings from patients who developed colds after RV challenge. RV14 and RV1A, major and minor receptor group RVs, respectively, were potent stimulators of IL-6 protein production in vitro. These effects were associated with significant increases in IL-6 mRNA accumulation and gene transcription. RV was also a potent stimulator of IL-6 promoter-driven luciferase activity. This stimulation was modestly decreased by mutation of the nuclear factor (NF) - IL-6 site and abrogated by mutation of the NF-κB site in this promoter. An NF-κB-DNA binding activity, mediated by p65, p50, and p52 NF-κB moieties, was rapidly induced in RV-infected cells. Activator protein 1-DNA binding was not similarly altered. These studies demonstrate that IL-6 is produced during symptomatic RV infections, that RVs are potent stimulators of IL-6 elaboration, and that RV stimulation of IL-6 production is mediated by an NF-κB-dependent transcriptional stimulation pathway. IL-6 may play an important role in the pathogenesis of RV infection, and NF-κB activation is likely to be an important event in RV-induced pathologies.

Original languageEnglish (US)
Pages (from-to)421-430
Number of pages10
JournalJournal of Clinical Investigation
Volume97
Issue number2
DOIs
StatePublished - Jan 15 1996

Keywords

  • Epithelial cell
  • Fibroblast
  • NF-IL-6
  • Upper respiratory tract infection

ASJC Scopus subject areas

  • Medicine(all)

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