Respiratory syncytial virus increases IL-8 gene expression and protein release in A549 cells.
The mechanism of respiratory syncytial virus (RSV)-induced inflammation in the airways of infants and children is not fully understood. We hypothesized that RSV directly induces interleukin (IL)-8 gene expression in airway epithelial cells, independent of IL-1 beta and tumor necrosis factor-alpha (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 2 h 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 nonreplicative RSV at the 2-h time point. Both active RSV and nonreplicative RSV increased the transcriptional activity of the 1.6-kb 5' flanking region of the IL-8 gene. Neither active RSV nor nonreplicative 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 h) but dependent on viral replication late (24 h).
Fiedler
M A
MA
Department of Pediatrics, Children's Hospital Research Foundation, Cincinnati, Ohio, USA.
Wernke-Dollries
K
K
Stark
J M
JM
D000818:Animals; D002522:Chlorocebus aethiops; D004355:Drug Stability; D015870:Gene Expression; D005796:Genes; D006801:Humans; D016209:Interleukin-8 / Q000235:genetics* / Q000378:metabolism*; D008175:Lung Neoplasms / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D018357:Respiratory Syncytial Virus Infections / Q000378:metabolism; D012136:Respiratory Syncytial Viruses / Q000254:growth & development / Q000502:physiology*; D013997:Time Factors; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured; D014779:Virus Replication
D016209:Interleukin-8; D012333:RNA, Messenger