STAT1 participates in the induction of substance P expression in airway epithelial cells by respiratory syncytial virus

objective: The regulation effect and mechanism of respiratory syncytial virus (RSV) infection on the expression of tachykinin substance P (SP) in airway epithelial cells was investigated. methods: The regulation of SP expression by RSV was investigated in the BEAS-2B airway epithelial cell line. RT-qPCR, immunofluorescence, and ELISA assay were used to examine the expression of the SP encoding gene , the intracellular SP protein expression, and the extracellular SP secretion. results: The mRNA expression of and the intracellular SP protein level in BEAS-2B cells were significantly enhanced by RSV infection with multiplicity of infection (MOI) values of both 1 and 0.1 at 48 hours post infection. Heat-inactivated and UV-inactivated RSV, but not live RSV, significantly induced SP secretion in both control BEAS-2B cells and CX3CR1 receptor knockout cells without affecting the gene expression or cell viability. RSV G protein (2-10 μg/ml) and fractalkine (10-50 ng/ml), both CX3CR1 receptor ligands, did not affect SP secretion in BEAS-2B cells. Inhibition of STAT1 phosphorylation by fludarabine (1 μM) markedly reduced the RSV-induced gene expression and antagonized the inhibition of RSV replication by interferon-α in BEAS-2B cells. conclusions: STAT1 participates in RSV infection-induced SP expression in airway epithelial cells.