RATIONALE: HRV is a major trigger of acute exacerbations of asthma and chronic obstructive pulmonary disease (COPD). Since NO exerts antiviral and antiinflammatory effects, we examined whether NO inhibits HRV-16-induced production from HAE of IP-10, a chemoattractant for type 1 T cells and natural killer cells, and studied the mechanisms underlying this inhibition. METHODS: Primary cultures of HAE, or the BEAS-2B human bronchial epithelial cell line, were exposed to HRV-16, or the replication intermediate double-stranded RNA (dsRNA), in the presence or absence of the NO donor, NONOate. BEAS-2B cells were transfected with IP-10 promoter-firefly luciferase constructs of varying lengths (both wild-type and containing point mutations in the AP-1, ISRE, NF-kB1 or NF-kB2 recognition sequences for these transcription factors). Cells were then infected with HRV-16 and the effects of NONOate examined. RESULTS: NONOate significantly inhibited IP-10 mRNA expression and protein release induced by HRV-16 or dsRNA from both BEAS-2B cells and HAE. NONOate inhibited IP-10 promoter activation by both HRV-16 and dsRNA. Studies with point mutants suggest that the ISRE, NF-kB1 and NF-kB2 are required for viral induction of promoter activity. Inhibition by NONOate also requires these sites and is not mediated by activation of soluble guanylyl cyclase. CONCLUSIONS: NO inhibits HRV-16- and dsRNA-induced IP-10 generation from epithelial cells by decreasing transcriptional activation. Inhibition of IP-10 promoter activity by NO appears to depend on the same sites needed by HRV-16 induction. Local delivery of NO may represent a potential therapeutic approach to control HRV-induced exacerbations of asthma and COPD.