MATUSO Muneaki Saga University, Faculty of Medicine, Assistant Prof, 助手 (20219398)
ICHIMARU Tomohiro Saga University, Faculty of Medicine, Assistant Prof, 助手 (80159847)
ZAITSU Masafumi Saga University, Faculty of Medicine, Assistant Prof, 助手 (10346877)
YAMAMOTO Shuichi Saga University, Faculty of Medicine, Assistant Prof, 助手 (30359947)
|Budget Amount *help
¥2,600,000 (Direct Cost : ¥2,600,000)
Fiscal Year 2004 : ¥700,000 (Direct Cost : ¥700,000)
Fiscal Year 2003 : ¥800,000 (Direct Cost : ¥800,000)
Fiscal Year 2002 : ¥1,100,000 (Direct Cost : ¥1,100,000)
Leukotrienes(LT) are very important lipid metabolites synthesized from membrane phospholipids by various internal and/or external stimuli, which play significant roles in the development of allergic inflammation in childhood asthma. It is an essential target to investigate the regulatory mechanisms of LT synthesizing and degrading enzymes as well as the function of receptors of these bioactive lipids. LT synthesizing enzymes are predominantly expressed in bone marrow-derived leukocytes. On the other hands, the degrading enzymes and receptors are widely distributed in various cell types, indicating a variety of patho-physiological roles of LTs in various organs.
Cultured human transformed bronchoepithelial cells were grown and incubated with various bioactive substances including Th2 cytokines such as IL-13,IL-10,IL-4 and IL-5,and then mRNA- and protein-expression of LT synthesizing and degrading enzymes ; cytosolic phospholipaseA2,5-lipoxygenase, LTA4-hydrolase, LTC4-synthase,5-LO-aetivating peptide, ganmma-glutamyl transpeptidase, ganmma-glutamyl transpeptidase related enzyme, and receptors of LTs ; cysteinyl LT receptor-1,cysteinyl LT receptor-2 and BLT were evaluated by RT-PCR and western blotting.
We have found that expression of cysteinyl LT receptor-1 is up-regulated by IL-13 and TNFa, which indicates that action of cysteinyl LTs are enhanced in Th2 cytokine dominant conditions through the transcriptional up-regulatory mechanism of the receptor.
We have also found that IL-4 and IL-13 predominantly induce eotaxin-3, a potent chemoattractant to eosinophils, in human bronchoepithelial cells. Interferon ganmma, a Th1 cytokine ; produced by viral infection, inhibits IL-13 induced eotaxin-3. These findings suggest that viral infection may be involved in pathogenesis of bronchial asthma.