| Budget Amount *help |
¥3,800,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥300,000)
Fiscal Year 2007: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2006: ¥2,500,000 (Direct Cost: ¥2,500,000)
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| Research Abstract |
We first examined the effect of IL-4, a Th2 cytokine, and IFN-g, a Th1 cytokine, on production of chemokine CCL26 in airway epithelial cells. IL-4 induced production of CCL26 from airway epithelial cells. IFN-g inhibited IL-4-induced CCL26 production when added simultaneously. On the other hands, prior stimulation with INF-g to airway epithelial cells enhanced IL-4-induced CCL26 production. This effect was resulted from up-regulation of IL-4 receptor system. IFN-g enhanced mRNA expression of both IL-4Ra and IL-2Rg. Flowcytometry analysis also revealed enhanced protein expression of IL-4Ra and IL-2Rg at cell surface. Enhanced expression of IL-4R leads to enhanced IL-4-induced CCL26 production through Jak-STAT signaling system.
Then, a model of airway virus infection was used to examine the mechanisms of virus-induced bronchial asthma exacerbations. Polyinocinic-citidiric acid (poly (IC)), a double-stranded RNA, was transfected to cultured airway epithelial cells including primary cells.
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By the transfection of poly (IC), airway epithelial cells produced IL-8 and RANTES suggesting that this model can be used as airway virus infection. Poly (IC) alone did not influence production of CCL26 from airway epithelial cells, however, IL-4-induced CCL26 production was significantly enhanced in poly (IC) -transfected cells. We also observed enhanced IL-4R by transfection of poly (IC) in airway epithelial cells. IL-4Ra and IL-2Rg chains were up-regulated in both mRNA and protein levels. Enhanced IL-4R expression resulted in enhanced production of CCL26.
These results might suggest that during virus infection, IFN-g produced from lymphocytes infiltrated to the airway triggered enhanced eosinophilic airway inflammation by enhanced production of CCL26 from airway epithelial cells. Virus infection itself also influences expression of IL-4R system. Thus, we speculated that virus airway infection might trigger not only neutrophilic airway infiltration but also eosinophilic airway infiltration. Less
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