Transcriptional induction of multiple cytokines by human respiratory syncytial virus requires activation of NF-kappa B and is inhibited by sodium salicylate and aspirin

Virology. 1997 Jun 9;232(2):369-78. doi: 10.1006/viro.1997.8582.


Infection of the lung epithelial cell line A549 by respiratory syncytial virus (RSV) resulted in the elevated synthesis of multiple cellular cytokines, including a number of interleukins (ILs). Detailed studies of IL-11 induction revealed that it required infection by viable virus and involved a net increase in the steady state level of IL-11 mRNA. Nuclear run-on assays showed a direct effect of RSV on IL-11 gene transcription. Mutational analysis of the IL-11 promoter fused to a reporter luciferase gene demonstrated the requirement of a region 720 nucleotides upstream of the mRNA start site in the transcriptional induction of IL-11 by RSV. Two nearly identical 10-nucleotide-long sequences GGGGTCTCCC and GGGTCTCCCC in this region resembled the NF-kappa B consensus motif. Mutation of either sequence greatly reduced RSV-mediated induction of IL-11 promoter activity. NF-kappa B sites in IL-1 alpha, IL-6, and IL-8 promoters were also required for RSV-mediated induction of transcription of these promoters. Immunological studies and use of reporter gene constructs provided direct evidence for the activation and nuclear translocation of NF-kappa B by RSV. Sodium salicylate and aspirin, inhibitors of NF-kappa B activation, abolished transcriptional induction of all these cytokines by RSV. Together, these studies demonstrated an essential role of NF-kappa B in RSV-mediated transcription of multiple cytokines genes and suggested a possible use of salicylates in managing airway inflammation and viral pathogenesis during RSV infection.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
  • Aspirin / pharmacology*
  • Cytokines / genetics*
  • Gene Expression Regulation / drug effects
  • Humans
  • Interleukin-1 / genetics
  • Interleukin-11 / genetics
  • Interleukin-6 / genetics
  • Interleukin-8 / genetics
  • NF-kappa B / genetics*
  • Promoter Regions, Genetic
  • Respiratory Syncytial Virus, Human / physiology*
  • Sodium Salicylate / pharmacology*
  • Transcription, Genetic*
  • Transcriptional Activation
  • Tumor Cells, Cultured


  • Anti-Inflammatory Agents, Non-Steroidal
  • Cytokines
  • Interleukin-1
  • Interleukin-11
  • Interleukin-6
  • Interleukin-8
  • NF-kappa B
  • Aspirin
  • Sodium Salicylate