Transcriptional activation of the interleukin-8 gene by respiratory syncytial virus infection in alveolar epithelial cells: Nuclear translocation of the RelA transcription factor as a mechanism producing airway mucosal inflammation

Roberto Garofalo, Mona Sabry, Mohammad Jamaluddin, Robert K. Yu, Antonella Casola, Pearay L. Ogra, Allan R. Brasier

Research output: Contribution to journalArticle

175 Scopus citations

Abstract

The most common cause of epidemic pediatric respiratory disease, respiratory syncytial virus (RSV), stimulates interleukin-8 (IL-8) synthesis upon infecting airway epithelium, an event necessary for the development of mucosal inflammation. We investigated the mechanism for enhanced IL-8 production in human A549 type II pulmonary epithelial cells. Infection with sucrose-purified RSV (pRSV) produced a time-dependent increase in the transcriptional initiation rate of the IL-8 gene. Transient transfection of the human IL-8 promoter mutated in the binding site fur nuclear factor-κB (NF-κB) demonstrated that this sequence was essential for pRSV-activated transcription. Gel mobility shift assays demonstrated pRSV induction of sequence-specific binding complexes; these complexes were supershifted only by antibodies directed to the potent NF-κB transactivating subunit RelA. Both Western immunoblot and indirect immunofluorescence assays showed that cytoplasmic RelA in uninfected cells became localized to the nucleus after pRSV infection. RelA activation requires replicating RSV, because neither conditioned medium nor UV-inactivated pRSV was able to stimulate its translocation. We conclude that RelA undergoes changes in subcellular distribution in airway epithelial cells upon pRSV infection. The ability of replicating RSV to activate RelA translocation may play an important rule in activating IL-8 and other inflammatory gene products necessary for airway mucosal inflammation seen in RSV disease.

Original languageEnglish (US)
Pages (from-to)8773-8781
Number of pages9
JournalJournal of Virology
Volume70
Issue number12
DOIs
StatePublished - Dec 1996

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

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