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Role of Bruton's tyrosine kinase in allergic reactions

布鲁顿酪氨酸激酶在过敏反应中的作用

基本信息

批准号：
10672045
负责人：
INAGAKI Naoki
金额：
$ 2.43万
依托单位：
Gifu Pharmaceutical University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1998
资助国家：
日本
起止时间：
1998 至 1999
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10672045/
关键词：
Bruton's tyrosine kinase Btk IgE allergic reaction XID mouse Bruton's tyrosine kinase Btk XIDマウスブルトン型チロシンキナーゼ CBA Nマウス XID

项目摘要

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.

为了阐明布鲁顿酪氨酸激酶（Btk）在过敏反应中的作用，我们研究了CBA/N （XID）小鼠和CBA/JxCBA/N F1雄性小鼠与对照小鼠、CBA/J和CBA/JxCBA/N F1雌性小鼠的一些实验性过敏反应。此外，利用反义寡核苷酸检测了Btk在培养的人肥大细胞释放介质中的作用。CBA/JxCBA/N F1雄性小鼠与雌性小鼠相比，二硝基氟苯诱导的ige依赖性三期皮肤反应均减少。与CBA/J小鼠相比，卵清蛋白免疫诱导的CBA/N小鼠的IgM产量明显较低，而CBA/N小鼠的IgE产量明显较高。CBA/J小鼠和CBA/N小鼠对促炎因子TNF-α、IL-1β和Il-6的产生与痤疮丙酸杆菌和脂多糖处理没有差异。培养的人肥大细胞在ige依赖性刺激后释放组胺、白三烯、前列腺素和细胞因子。在本研究中，我们在刺激前用反义寡核苷酸处理培养的人肥大细胞一周。组胺释放和GM-CSF的产生不受治疗的影响。在目前的实验条件下，反义寡核苷酸可能无法有效地导入肥大细胞。我们需要在不同的实验条件下进行额外的实验。这些结果和去年获得的先前数据表明，由于肥大细胞激活不足，XID小鼠的ige依赖性过敏反应减弱。Btk可能对巨噬细胞谱系的激活没有贡献。此外，反复使用半抗原引起的皮肤反应和IgE的产生可能受到Btk的调节，因为这些反应在XID小鼠中增加。