Respiratory syncytial virus increases il-8 gene expression and
protein release in a549 cells.
Fiedler, Michael A., Kara Wernke-Dollries, and James M. Stark.
Division of Pulmonary Medicine, Department of Pediatrics,
Children's Hospital Research Foundation and University of Cincinnati,
College of Medicine, Cincinnati, Ohio, 45229-3039
APStracts 2:0161L, 1995.
The mechanism of RSV induced inflammation in the airways of infants
and children is not fully understood. We hypothesized that RSV
directly induces interleukin-8 (IL-8) gene expression in airway
epithelial cells, independent of IL-1[beta] and TNF[alpha]
production. Exposure of A549 cells (an airway epithelial cell line)
to RSV resulted in increased IL-8 mRNA expression and IL-8 protein
release from the cells as early as two hours after treatment. Neither
IL-1[beta] nor TNF[alpha] (mRNA or protein) were detected. Viral
replication was not necessary for the effects of RSV on IL-8 mRNA
expression and protein release early in the infectious process.
However, sustained levels of increased IL-8 production required RSV
replication. A dose response relationship was observed between the
multiplicity of infection and IL-8 production with both active and
non-replicative RSV at the two hour time point. Both active RSV and
non-replicative RSV increased the transcriptional activity of the 1.6
kilobase 5' flanking region of the IL-8 gene. Neither active RSV nor
non-replicative RSV increased the stability of the IL-8 mRNA in A549
cells. We conclude that RSV increases IL-8 gene expression in A549
cells in a biphasic pattern independent of viral replication early (2
hours), but dependent on viral replication late (24 hours).
Received 28 February 1995; accepted in final form 19 July 1995.
APS Manuscript Number L63-5.
Article publication pending Am. J. Physiol. (Lung Cell. Mol.
Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 23 September 1995.