Comprehensive analysis of mRNA expression profiles in human respiratory epithelial cells after inoculation with respiratory syncytial virus

Abstract

Rationale Bronchiolitis in infancy, especially caused by Respiratory Syncytial Virus (RSV) infection, is thought to increase the risks for allergic sensitization and recurrent wheezing later in life. To investigate how RSV infection elicit immune changes in the host, mRNA expression profiles in human respiratory epithelial cells after inoculation with RSV were analyzed comprehensively. Methods Human A549 cells were inoculated with RSV (long strain) or UV-treated RSV. Total RNA was extracted from the cells at different time points, and mRNA expression profiles were assessed by an oligonucleotide probe-array system (GeneChip, Affymetrix). Results After 24 hours of culture, expression of approximately 219 out of 18,000 genes were judged increased in RSV infected cells when compared with that in cells cultured with UV-treated RSV (>2-fold by normalized data). After hierarchical clustering analysis, several gene clusters were identified. Those included type I IFN-inducible genes (Mx1, IFIT1, OAS2), pro-inflammatory cytokine genes (IL-6, TNF-α, IL-1β) and chemokines genes (IL-8, RANTES, MCP-3). However, mRNA levels for Th2 cell-attracting chemokines (TARC, MDC, or I-309) were not changed. Conclusions Out results suggest that RSV infection induces host immune responses such as inflammatory reactions through production of immunomodulatory mediators from respiratory epithelial cells.