Requirement of a novel upstream response element in respiratory syncytial virus-induced IL-8 gene expression

Antonella Casola, Roberto Garofalo, Mohammad Jamaluddin, Spiros Vlahopoulos, Allan R. Brasier

Research output: Contribution to journalArticle

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Abstract

Respiratory syncytial virus (RSV) produces intense pulmonary inflammation, in part, through its ability to induce chemokine synthesis in infected airway epithelial cells. In this study, we compare mechanisms for induction of the CXC chemokine IL-8, in human type II alveolar (A549) cells by RSV infection and by stimulation with the cytokine TNF. Promoter deletion and mutagenesis experiments indicate that although the region from -99 to -54 nt is sufficient for TNF-induced IL-8 transcription, this region alone is not sufficient for RSV-induced IL-8 transcription. Instead, RSV requires participation of a previously unrecognized element, spanning from -162 to - 132 nt, that we term the RSV response element (RSVRE), and a previously characterized element at -132 to -99 nt, containing an AP-1 binding site. RSV infection of A549 cells induces increased RSVRE- and AP-1-binding activities and increased synthesis of IFN regulatory factor-1 protein, which is present in the RSVRE-binding complex. These data confirm that the IL-8 gene enhancers are controlled in a stimulus-specific fashion and participation of distinct promoter elements is required to activate gene transcription. These observations are important for rational design of inhibitors of RSV-induced lung inflammation.

Original languageEnglish (US)
Pages (from-to)5944-5951
Number of pages8
JournalJournal of Immunology
Volume164
Issue number11
StatePublished - 2000

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Respiratory Syncytial Viruses
Response Elements
Interleukin-8
Gene Expression
Respiratory Syncytial Virus Infections
Transcription Factor AP-1
Pneumonia
Alveolar Epithelial Cells
CXC Chemokines
Chemokines
Mutagenesis
Genes
Epithelial Cells
Binding Sites
Cytokines
Proteins

ASJC Scopus subject areas

  • Immunology

Cite this

Requirement of a novel upstream response element in respiratory syncytial virus-induced IL-8 gene expression. / Casola, Antonella; Garofalo, Roberto; Jamaluddin, Mohammad; Vlahopoulos, Spiros; Brasier, Allan R.

In: Journal of Immunology, Vol. 164, No. 11, 2000, p. 5944-5951.

Research output: Contribution to journalArticle

Casola, Antonella ; Garofalo, Roberto ; Jamaluddin, Mohammad ; Vlahopoulos, Spiros ; Brasier, Allan R. / Requirement of a novel upstream response element in respiratory syncytial virus-induced IL-8 gene expression. In: Journal of Immunology. 2000 ; Vol. 164, No. 11. pp. 5944-5951.
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