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,
Departments of
*
Pediatrics and
Internal Medicine and
Sealy Center for Molecular Sciences, University of Texas Medical Branch, Galveston, TX 77555
Respiratory syncytial virus (RSV) produces intense pulmonary inflammation, in part, through its ability to induce chemokine synthesis in infected airway 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 infection and by stimulation with the cytokine TNF. Promoter deletion and mutagenesis experiments indicate that although the region from -99 to -54 nt is sufficient for TNF-induced IL-8 transcription, this region alone is not sufficient for RSV-induced IL-8 transcription. Instead, RSV requires participation of a previously unrecognized element, spanning from -162 to -132 nt, that we term the RSV response element (RSVRE), and a previously characterized 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 increased synthesis of IFN regulatory factor-1 protein, which is present in the RSVRE-binding complex. These data confirm that the IL-8 gene enhancers are controlled in a stimulus-specific fashion and participation of distinct promoter elements is required to activate gene transcription. These observations are important for rational design of inhibitors of RSV-induced lung inflammation.
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M. Nourbakhsh, S. Kalble, A. Dorrie, H. Hauser, K. Resch, and M. Kracht The NF-kappa B Repressing Factor Is Involved in Basal Repression and Interleukin (IL)-1-induced Activation of IL-8 Transcription by Binding to a Conserved NF-kappa B-flanking Sequence Element J. Biol. Chem., February 2, 2001; 276(6): 4501 - 4508. [Abstract] [Full Text] [PDF]
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A. Casola, N. Burger, T. Liu, M. Jamaluddin, A. R. Brasier, and R. P. Garofalo Oxidant Tone Regulates RANTES Gene Expression in Airway Epithelial Cells Infected with Respiratory Syncytial Virus. ROLE IN VIRAL-INDUCED INTERFERON REGULATORY FACTOR ACTIVATION J. Biol. Chem., June 1, 2001; 276(23): 19715 - 19722. [Abstract] [Full Text] [PDF]
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