| Budget Amount *help |
¥3,800,000 (Direct Cost: ¥3,800,000)
Fiscal Year 1999: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1998: ¥2,900,000 (Direct Cost: ¥2,900,000)
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| Research Abstract |
To elucidate the role of Bruton's tyrosine kinase (Btk) in allergic reactions, we investigated some experimental allergic reactions in CBA/N (XID) mice and CBA/JxCBA/N F1 male mice comparing to their control mice, CBA/J and CBA/JxCBA/N F1 female mice. Furthermore, antisense oligonucleotide was employed to examine the role of Btk in mediator release from cultured human mast cells.
All three phases of dinitrofluorobenzene-induced IgE-dependent triphasic cutaneous reaction was reduced in CBA/JxCBA/N F1 male mice comparing to female mice. IgM production in CBA/N mice induced by ovalbumin immunization was apparently low in comparison with CBA/J mice, whereas IgE production was apparently high in CBA/N mice. There was no difference between CBA/J and CBA/N mice in production of proinflammatory cytokines, TNF-α, IL-1β and Il-6, caused by treatments with Propionibacterium acnes and lipopolysaccharide.
Cultured human mast cells release histamine, leukotrienes, prostaglandins and cytokines after IgE-dependent stimulation. In the present study, we treated cultured human mast cells with antisense oligonucleotide for a week before the stimulation. Histamine release and GM-CSF production were not affected by the treatment. In the present experimental condition, antisense oligonucleotide might not be introduced into mast cells effectively. We need additional experiments using different experimental conditions.
These results and previous data obtained last year suggest that IgE-dependent allergic reactions wane in XID mice because of inadequate activation of mast cells. Btk may not contribute the activation of cells of macrophage lineage. Furthermore, cutaneous reaction caused by repeated application with hapten and IgE production may be regulated by Btk, because these responses are increased in XID mice.
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