Cell type-specific mechanisms of interleukin-8 induction by dengue virus and differential response to drug treatment.
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.
Center for Infectious Disease and Vaccine Research and Department of Medicine, University of Massachusetts Medical School, Worcester 01655, USA.
Carey L
CL
Medin
Alan L
AL
Rothman
D002460:Cell Line; D045744:Cell Line, Tumor; D004274:DNA, Recombinant; D003715:Dengue / Q000188:drug therapy / Q000276:immunology*; D003716:Dengue Virus / Q000187:drug effects / Q000502:physiology*; D003907:Dexamethasone / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D015870:Gene Expression / Q000187:drug effects; D017930:Genes, Reporter; D005938:Glucocorticoids / Q000494:pharmacology; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D016209:Interleukin-8 / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000378:metabolism*; D008156:Luciferases / Q000032:analysis; D016328:NF-kappa B / Q000378:metabolism; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D020889:Rolipram / Q000494:pharmacology; D018808:Transcription Factor AP-1 / Q000378:metabolism
D004274:DNA, Recombinant; D004791:Enzyme Inhibitors; D005938:Glucocorticoids; D007093:Imidazoles; D016209:Interleukin-8; D016328:NF-kappa B; D010726:Phosphodiesterase Inhibitors; D011725:Pyridines; D018808:Transcription Factor AP-1; D003907:Dexamethasone; D008156:Luciferases; D020889:Rolipram; C093642:SB 203580