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Title: The regulation of nitric oxide by intracellular glutathione in lung epithelial cells
Author: Watchorn, Tammy
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 1998
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The hypothesis of this thesis is that changes in intracellular GSH redox state effect iNOS mRNA, via NF-κB activation, in response to both cytokines and oxidants. The data presented show that both cytokines and oxidants (H2O2) induce iNOS mRNA and NO release in both the human Alveolar Type II epithelial cell line (A549) and the human Bronchial Epithelial cell line (16HBE14o-) and this NO release is concomitant with a decrease in GSH. The decrease in GSH is not, however, due to the production of NO as shown by the use of NO inhibitors supporting a role for GSH in NO induction. Decreasing intracellular GSH levels with BSO caused an increase in iNOS induction and NO release suggesting decreased GSH levels may have a role in iNOS induction. GSH levels were increased by 4 thiol compounds to determine if increased GSH levels could prevent or decrease iNOS induction. Increased GSH levels decreased H2O2 induction, but not cytomix induction of NF-κB activation and NO. release. This suggests that increasing oxidant stress directly, using an oxidant, results in NF-κB activation and iNOS induction, and this increase can be inhibited by increasing intracellular GSH levels. Increasing NO. release and NF-κB activation with a mixture of cytokines is not, however, decreased by increased GSH levels, suggesting an alternate pathway exists for NF-κB activation and iNOS induction by cytomix. In conclusion, this data supports the hypothesis that the redox status of the cell, particularly GSH, is involved in the activation of NF-κB and induction of iNOS by oxidants. These data may be important in inflammatory disorders of the lung and may provide information on the uses of antioxidants as a means of inhibiting NO. during lung inflammation.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available