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INHIBITION OF RESPIRATORY SYNCYTIAL VIRUS (RSV)-INDUCED INFLAMMATION BY 3-NITROTYROSINE IN HUMAN BRONCHIAL EPITHELIAL CELLS
Soukup, J M., Huang, YuhChin T, AND Z. Li. INHIBITION OF RESPIRATORY SYNCYTIAL VIRUS (RSV)-INDUCED INFLAMMATION BY 3-NITROTYROSINE IN HUMAN BRONCHIAL EPITHELIAL CELLS. Presented at American Thoracic Society Meeting, Orlando, FL, May 21-26, 2004.
Inhibition of Respiratory Syncytial Virus (RSV)-Induced Inflammation by 3-Nitrotyrosine in Human Bronchial Epithelial Cells. J. M. Soukup, MPH 1, ZW. Li, MD 2 and YC. T. Huang, MD 1. 1 NHEERL, US Environmental Protection Agency, RTP, NC and 2 CEMALB, University of North Carolina, Chapel Hill, NC .
3-Nitrotyrosine (NO2Tyr), a nitration product of free tyrosine, can be produced during nitrosative and oxidative stress, such as exposure to nitrogen dioxide (NO2). NO2 exposure induces pulmonary infiltration of neutrophils that can produce nitrating species from myeloperoxidase-mediated H2O2-nitrite reaction. We showed previously that NO2Tyr can be incorporated into -tubulin posttranslationally in human bronchial epithelial cells and nitrotyrosination of -tubulin inhibits RSV-induced RANTES release. In this study, we investigated the mechanisms by which nitrotyrosination of -tubulin inhibits RSV infection. Supplementation of culture medium with NO2Tyr dose-dependently inhibited RSV-induced RANTES production and viral release by human bronchial epithelial (BEAS-2B) cells. 3-Chlorotyrosine, another neutrophil myeloperoxidase reaction product, had no effect alone but reversed the NO2Tyr-induced inhibition on RANTES production. Heparin, an inhibitor of caseine kinase II (CKII) which is involved in RSV transcriptional activity and which copolymerizes with tubulin, blocked RSV-induced RANTES production more effectively than its direct viricidal effects. The amount of CKII co-precipitating with -tubulin was not affected by NO2Tyr. RSV released from NO2Tyr-treated cells showed increased serine phosphorylation of P and M proteins. TNF /IFN -induced release of RANTES was also inhibited by heparin but not by NO2Tyr. Pre-exposure of BEAS-2B cells to 1.5 ppm NO2 for 4 hours increased tyrosine nitration of proteins, including -tubulin, but had no effect on RSV-induced RANTES production or viral release. These results indicate that posttranslational nitrotyrosination of -tubulin inhibits RSV-specific RANTES release mediated by CKII. The exact site of inhibition was unclear but was not due to inhibition on viral transcriptional activity or non-specific tyrosine nitration of cellular proteins. (Abstract does not reflect USEPA policy).
Record Details:Record Type: DOCUMENT (PRESENTATION/ABSTRACT)
Organization:U.S. ENVIRONMENTAL PROTECTION AGENCY
OFFICE OF RESEARCH AND DEVELOPMENT
NATIONAL HEALTH AND ENVIRONMENTAL EFFECTS RESEARCH LABORATORY
HUMAN STUDIES DIVISION
CLINICAL RESEARCH BRANCH