Requirement of a novel upstream response element in respiratory syncytial virus-induced IL-8 gene expression

Respiratory syncytial virus (RSV) produces intense pulmonary inflammation, in part, through its ability to induce chemokine synthesis in infected airw ay epithelial. cells. In this study, we compare mechanisms for induction of the CXC chemokine IL-8, in human type II alveolar (A549) cells by RSV infe ction and by stimulation with the cytokine TNF. Promoter deletion and mutag enesis experiments indicate that although the region from -99 to -54 nt is sufficient for TNF-induced IL-8 transcription, this region alone is not suf ficient for RSV-induced IL-8 transcription. Instead, RSV requires participa tion of a previously unrecognized element, spanning from -162 to -132 nt, t hat we term the RSV response element (RSVRE), and a previously characterize d element at -132 to -99 nt, containing an AP-1 binding site. RSV infection of A549 cells induces increased RSVRE- and AP-1-binding activities and inc reased synthesis of IFN regulatory factor-1 protein, which is present In th e RSVRE-binding complex These data confirm that the IL-8 gene enhancers are controlled in a stimulus-specific fashion and participation of distinct pr omoter elements is required to activate gene transcription. These observati ons are important for rational design of inhibitors of RSV-induced lung inf lammation.