| Budget Amount *help |
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2003: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2002: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Research Abstract |
Induction of inducible nitric oxide synthase m RNA (iNOS mRNA), xanthine oxidase mRNA (XO mRNA) and cylooxygenase-2 mRNA (COX-2 mRNA) in cultured human nasal epithelial cells were studied by exposing to 10^<-8>M leukotrien D_4(LTD_4) and 10^<-8>M platelet activating factor (PAF), respectively and 20 hours later total RNA was extracted. Each mRNA was investigated by real time -PCR. The concentration of the iNOS protein in the cell solution was also measured in a duplicate manner.
Results : (1)Comparing PBS, LTD_4 showed the same level induction of iNOS mRNA, XO mRNA and COX-2 mRNA. (2)Comparing PBS, PAF showed the same level induction of iNOS mRNA although PAF did higher level of induction of both XO mRNA and COX-2 mRNA. (3)LTD_4 augmented the concentration of the iNOS protein in the cell solution, while PAF did slightly.
These results suggest that LTD_4 may take part in excessive production of NO via iNOS, and PAF may do superoxide production via XO. These lipid mediators generated in su
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ch inflamed cells as eosinophils, neutrophils and macrophages ; especially PAF is generated in eosinophils in greater amount. Therefore, epithelial cells may also relate with excess production of NO and superoxide in allergic inflammation process.
These results suggest that LTD_4 and PAF released from inflamed cells such as eosinophils, other leukocytes takes part in superoxide production associated with other promoting factors of XO. It has been well known that inflamed cells produce superoxide, however, its mechanism has not been elucidated. LTB_4 has also the capacity of promoting superoxide generation in leukocytes. Therefore, under excessive generation of NO and superoxide generation, these molecules react each other generating peroxynitrite, which has strong injurious activity and attack tyrosine leaving a trace, nitrotyrosine. Our previous study showed nitrotyrosine in nasal leverage fluids of allergic patients with rhinitis. In the further study the effect of primary cytokines on induction of iNOS mRNA, XO mRNA and COX-2 mRNA in cultured human nasal epithelial cells should be elucidated. Less
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