Respiratory syncytial virus infection modulates interleukin‑8 production in respiratory epithelial cells through a transcription factor‑activator protein‑1 signaling pathway

Mol Med Rep. 2014 Sep;10(3):1443-7. doi: 10.3892/mmr.2014.2357. Epub 2014 Jun 26.

Abstract

Respiratory syncytial virus (RSV) is a leading cause of respiratory duct infection that can result in severe clinical symptoms, particularly among children under 3 years of age. In the current study, the effect of RSV on airway epithelial cell function and the potential signaling pathways involved were investigated. A549 human airway epithelial cells were infected with RSV at a multiplicity of infection of 1. After 24 h, interleukin (IL)‑8 secretion in the cell supernatant was analyzed. A microarray assay of RSV‑infected A549 cells was conducted in order to identify any potential pathways involved, and quantitative polymerase chain reaction was performed to examine mRNA expression levels in these pathways. Electrophoretic mobility shift assays of nuclear transcription factors were conducted for further verification. IL‑8 levels increased significantly in the supernatant of RSV‑infected A549 cells compared with levels in non‑infected cells. Microarray data suggested the involvement of the Toll‑like receptor 4 (TLR4) pathway, and mRNA expression levels of genes (MYD88, TRAM and TRIF) involved in this pathway were higher in infected cells. Enhanced synthesis of activator protein‑1 (AP‑1) was observed. RSV infection of A549 cells may promote IL‑8 secretion. In conclusion, the results of the present study indicate that the TLR4 signaling pathway, in conjunction with MYD88, TRAM, TRIF and the transcription factor AP‑1, may activate immune responses to RSV infection in airway epithelial cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Activating Transcription Factor 1 / genetics*
  • Activating Transcription Factor 1 / metabolism
  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / metabolism
  • Adaptor Proteins, Vesicular Transport / genetics
  • Adaptor Proteins, Vesicular Transport / metabolism
  • Cell Line, Tumor
  • Epithelial Cells / metabolism*
  • Humans
  • Interleukin-8 / metabolism*
  • Microarray Analysis
  • Myeloid Differentiation Factor 88 / genetics
  • Myeloid Differentiation Factor 88 / metabolism
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Respiratory Syncytial Virus Infections / pathology*
  • Respiratory Syncytial Viruses
  • Signal Transduction*

Substances

  • ATF1 protein, human
  • Activating Transcription Factor 1
  • Adaptor Proteins, Signal Transducing
  • Adaptor Proteins, Vesicular Transport
  • Interleukin-8
  • MYD88 protein, human
  • Myeloid Differentiation Factor 88
  • RNA, Messenger
  • TICAM1 protein, human
  • TICAM2 protein, human