Skip to main content
Article
Increased production of interleukin-8 in primary human monocytes and in human epithelial and endothelial cell lines after dengue virus challenge
GSBS Student Publications
  • Irene Bosch, University of Massachusetts Medical School
  • Kris Xhaja
  • Luis Estevez
  • Gregory Raines
  • Heather J. Melichar, University of Massachusetts Medical School
  • Rajas V. Warke, University of Massachusetts Medical School
  • Marcia V. Fournier
  • Francis A. Ennis, University of Massachusetts Medical School
  • Alan L. Rothman, University of Massachusetts Medical School
GSBS Program
Biochemistry & Molecular Pharmacology
UMMS Affiliation
Graduate School of Biomedical Sciences; Center for Infectious Disease and Vaccine Research; Department of Medicine, Division of Infectious Diseases and Immunology; Department of Pathology
Date
5-7-2002
Document Type
Article
Medical Subject Headings
Animals; Cell Line, Transformed; Cercopithecus aethiops; Culture Media; Dengue Virus; Endothelium, Vascular; Epithelial Cells; *Gene Expression; Humans; Interleukin-8; Monocytes; RNA, Messenger; Reverse Transcriptase Polymerase Chain Reaction; Transcription, Genetic; Vero Cells
Abstract
The more severe form of dengue virus infection, dengue hemorrhagic fever, is characterized by plasma leakage and derangements in hemostasis. As elevated interleukin-8 (IL-8) levels have been observed in sera from patients with more severe disease manifestations, a study was initiated to look at the effect of dengue virus infection in vitro on proinflammatory cytokine secretion and expression. A significant increase in IL-8 levels in the culture supernatant of primary human monocytes infected with dengue 2 virus (D2V) New Guinea C (NGC) was found by enzyme-linked immunosorbent assay. Additionally, by reverse transcriptase PCR, the mRNA was also augmented. Among the proinflammatory cytokines and their mRNAs measured (IL-6, IL-1 beta, IL-8, and tumor necrosis factor alpha), IL-8 showed the greatest change following D2V infection. Similarly, two cell lines, 293T (a human epithelial cell line) and ECV304 (an endothelial cell line), were permissive to D2V NGC and responded to the infection by increasing the synthesis of IL-8. Nuclear factor kappa B (NF-kappa B) and nuclear factor IL-6 (NFIL-6) are primary mediators of IL-8 expression. We studied the transcriptional regulation of IL-8 in the ECV304 and 293T cell lines and found that the induction of IL-8 gene expression involved the activation of NF-kappa B (P = 0.001) and, to a lesser extent, the activation of NFIL-6 in ECV304 cells only. We next observed by the chromatin immunoprecipitation procedure in vivo acetylation of core histones bound to the IL-8 promoter after D2V infection. IL-8 produced by infected monocytes and also IL-8 that may be produced by endothelial or other epithelial cells is associated with the hyperacetylation of histones bound to the IL-8 promoter in addition to the activation of transcription by NF-kappa B. We hypothesize that the overall increase in IL-8 synthesis observed in this in vitro study may play a role in the pathogenesis of the plasma leakage seen in dengue hemorrhagic fever and dengue shock syndrome.
Rights and Permissions
Citation: J Virol. 2002 Jun;76(11):5588-97.
Related Resources
Link to article in PubMed
PubMed ID
11991987
Citation Information
Irene Bosch, Kris Xhaja, Luis Estevez, Gregory Raines, et al.. "Increased production of interleukin-8 in primary human monocytes and in human epithelial and endothelial cell lines after dengue virus challenge" Vol. 76 Iss. 11 (2002) ISSN: 0022-538X (Print)
Available at: http://works.bepress.com/alan_rothman/20/