Interleukin-8 gene regulation in intestinal epithelial cells infected with rotavirus: Role of viral-induced IκB kinase activation

Antonella Casola, Roberto P. Garofalo, Sue E. Crawford, Mary K. Estes, Frank Mercurio, Sheila E. Crowe, Allan R. Brasier

Research output: Contribution to journalArticle

49 Scopus citations

Abstract

Rotavirus is the major etiologic agent of diarrhea in children and the most common cause of severe pediatric gastroenteritis. Rotavirus infection is limited to mature enterocytes that line the villi of the small intestine. Gut epithelial cells, upon infection and cytokine stimulation, are able to produce chemokines, a family of small chemotactic cytokines that regulate the migration and activation of leukocytes. We have previously shown that rotavirus infection of the intestinal epithelial cell line HT-29 induces increased expression of the CXC chemokine interleukin- (IL) 8. Mechanisms responsible for the transcriptional regulation of the IL-8 gene in intestinal epithelial cells during viral infections have not been fully elucidated. Therefore, the purpose of this study was to define the molecular mechanisms of IL-8 gene expression in HT-29 cells infected with rotavirus. Transient transfection analysis of 5′ deletions and mutations of the IL-8 promoter driving expression of luciferase reporter gene indicates that the activating protein- (AP) 1 and nuclear factor- (NF) κB elements are necessary for IL-8 promoter activation during rotavirus infection. The importance of NF-κB activation for IL-8 gene expression was further demonstrated by the inhibition of rotavirus-induced IL-8 gene transcription and protein synthesis following blockade of degradation of the NF-κB cytoplasmic inhibitor IκB-α. Rotavirus infection of HT-29-induced IκB kinase (IKK) activation and overexpression of a dominant negative mutant of IKK-β greatly reduced rotavirus-induced IL-8 promoter activation and NF-κB-driven transcription, indicating that IKK is involved in rotavirus-induced IL-8 gene expression and NF-κB activation.

Original languageEnglish (US)
Pages (from-to)8-19
Number of pages12
JournalVirology
Volume298
Issue number1
DOIs
StatePublished - 2002

ASJC Scopus subject areas

  • Virology

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