|Budget Amount *help
¥2,600,000 (Direct Cost: ¥2,600,000)
Fiscal Year 2002: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 2001: ¥1,800,000 (Direct Cost: ¥1,800,000)
Nitric oxide (NO) is believed to participate in regulation of airway clearance and nonspecific cellular immunity in human airways. A large amount of NO is continuously produced in the nasal airway, and surface epithelial cells of human paranasal sinuses seem to be the dominant source of local NO production. In the present study, we have investigated functional roles of nitric oxide in human nose and paranasal sinuses in relation to regulatory mechanisms by transcription factors.
1) We examined the difference in NO production in human nasal epithelial cells between normal subjects and patients with perennial allergic rhinitis (AR), and to assess relationship between expression of nitric oxide synthase (NOS) isoforms and severity of the disease. AR patients overall produced higher levels of NO through the concomitant expression of different NOS isoforms. Nasal epithelial cells have the potential ability to express iNOS protein spontaneously or upon stimulation with inflammatory cytokines,
such as IFN-gamma and TNF-alpha. In addition, the use of DAF-2 DA, a real-time NO indicator, provided a reliable method to visualize and quantify the direct NO production of living cells.
2) We examined the activation of nuclear factor-kappa B (NF-kB), one of the most important transcription factors in various inflammatory diseases, in human nasal polyps, and assessed the relationship between the degree of activation and local cytokine gene expression. Significant correlations were observed between the degree of epithelial NF-kB activation and the levels of 1L-8, IL-16, and eotaxin mRNA expression. The activation of NF-kB in the nasal polyp epithelium is responsible for the recruitment of inflammatory cells, particularly eosinophils, through the initiation of the transcriptional pathway of the related cytokines. Because the high level of exhaled NO is considered as a potential marker of allergic airway inflammation, preserving iNOS gene from its unregulated induction may be important for maintenance of nasal homeostasis and may offer a tool of therapeutic intervention. Less