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NITROTYROSINE ATTENUATES RSV-INDUCED INFLAMMATION IN AIRWAY EPITHELIAL CELLS
Soukup, J M., Z. Li, S E. Becker, AND Huang, YuhChin T. NITROTYROSINE ATTENUATES RSV-INDUCED INFLAMMATION IN AIRWAY EPITHELIAL CELLS. Presented at American Thoracic Society Meeting, Seattle, Washington, May 16-21, 2003.
Nitrotyrosine attenuates RSV-induced inflammation in airway epithelial cells. Joleen Soukup, Zuowei Li, Susanne Becker and Yuh-Chin Huang. NHEERL, ORD, USEPA, RTP, North Carolina, CEMALB, University of North Carolina, Chapel Hill, North Carolina
Nitrotyrosine (NO2Tyr) is a naturally-occurring tyrosine analog whose concentration in bronchial lining fluid can increase during acute inflammation. Besides being a marker of oxidative-nitrosative stress, the biological function of nitrotyrosine remains unclear. Nitrotyrosine can be incorporated irreversibly into alpha-tubulin post-translationally by tubulin-tyrosine ligase, and impair microtubular function. Since microtubules may be involved in the intracellular processing of viral particles, we hypothesized that nitrotyrosine may attenutate inflammation induced by respiratory syncytial virus (RSV). Bronchial epithelial cells (BEAS-2B) were pre-incubated with or without NO2Tyr (10-100 microM) for 24 hrs prior to incubation with RSV at 0.1, 0.3 and 1.0 MOI for 72 hours. Release of IL-6, IL-8, RANTES and TNF-alpha were measured at 24, 48 and 72 hours by ELISA. Nitrotyrosine attenuated RSV-induced release of IL-8 and RANTES by 50%. The titers of RSV were lower at all time points in media containing NO2Tyr. NO2Tyr had no direct virucidal effect as measured by HEp-2 plaque assay nor did it affect cell viability. Immunoprecipitation and immunoblotting with alpha-tubulin antibody and anti-NO2Tyr antibody showed a time-dependent increase in nitration of alpha-tubulin in BEAS cultured in NO2Tyr-supplemented media. Fluorescent imaging showed decreased intracellular FITC-tagged RSV. These results indicate that NO2Tyr attenuated RSV-induced chemokine release and this inhibition was associated with nitrotyrosination of alpha-tubulin.
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Record Details:Record Type: DOCUMENT (PRESENTATION/ABSTRACT)
Organization:U.S. ENVIRONMENTAL PROTECTION AGENCY
OFFICE OF RESEARCH AND DEVELOPMENT
NATIONAL HEALTH AND ENVIRONMENTAL EFFECTS RESEARCH LAB
HUMAN STUDIES DIVISION
CLINICAL RESEARCH BRANCH