Cell type-specific mechanisms of interleukin-8 induction by dengue virus and differential response to drug treatment
Graduate School of Biomedical Sciences; Center for Infectious Disease and Vaccine Research and Department of Medicine, Division of Infectious Diseases and Immunology
Medical Subject Headings
Cell Line; Cell Line, Tumor; DNA, Recombinant; Dengue; Dengue Virus; Dexamethasone; Enzyme Inhibitors; Enzyme-Linked Immunosorbent Assay; Gene Expression; Genes, Reporter; Glucocorticoids; Humans; Imidazoles; Interleukin-8; Luciferases; NF-kappa B; Phosphodiesterase Inhibitors; Pyridines; Rolipram; Transcription Factor AP-1
Life Sciences | Medicine and Health Sciences
In vitro infection with dengue virus induces interleukin (IL)-8 secretion, which increases endothelial cell permeability; this has been proposed as a mechanism for plasma leakage in dengue hemorrhagic fever. We studied the mechanisms of IL-8 induction, using luciferase reporter constructs, and the effect of pharmacological inhibitors of either IL-8 secretion or nuclear factor- kappa B (NF-kappa B) activation on IL-8 induction by dengue 2 virus (DEN2V) infection. IL-8 induction by DEN2V infection was associated with activation of NF- kappa B and activator protein-1 (AP-1) in HEK293A cells but only with activation of AP-1 in HepG2 cells. Treatment with SB203580, a mitogen-activated protein kinase inhibitor, and rolipram, a phosphodiesterase IV inhibitor, partially inhibited DEN2V-induced IL-8 secretion in HEK293A cells but increased DEN2V-induced IL-8 secretion in HepG2 cells. In contrast, treatment with dexamethasone increased DEN2V-induced IL-8 secretion in HEK293A cells but had no effect on DEN2V-induced IL-8 secretion in HepG2 cells. These results demonstrate that anti-inflammatory drugs have variable effects on IL-8 secretion in different cell types during DEN2V infection.
Rights and Permissions
Citation: J Infect Dis. 2006 Apr 15;193(8):1070-7. Epub 2006 Mar 6. Link to article on publisher's site
DOI of Published Version
The Journal of infectious diseases
Medin, Carey L. and Rothman, Alan L., "Cell type-specific mechanisms of interleukin-8 induction by dengue virus and differential response to drug treatment" (2006). GSBS Student Publications. 845.