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 雄性小鼠的一些实验性过敏反应，并与对照小鼠 CBA/J 和 CBA/ 进行比较。此外，采用反义寡核苷酸检测 JxCBA/N F1 雌性小鼠中 Btk 在培养的人肥大细胞介质释放中的作用。与雌性小鼠相比，CBA/JxCBA/N F1 雄性小鼠中二硝基氟苯诱导的 IgE 依赖性三相皮肤反应减少，卵清蛋白免疫诱导的 CBA/N 小鼠 IgM 产生明显低于 CBA/J 小鼠，而 IgE 产生明显较低。 CBA/N 小鼠中的促炎细胞因子、TNF-α、CBA/J 和 CBA/N 小鼠的产生没有差异。 IL-1β和IL-6，由痤疮丙酸杆菌和脂多糖处理引起。培养的人类肥大细胞在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，我们用反义寡核苷酸处理培养的人类肥大细胞。刺激前一周，组胺释放和 GM-CSF 产生不受治疗影响。我们需要使用不同的实验条件进行额外的有效实验。这些结果和去年获得的数据表明，由于肥大细胞激活不足，IgE 依赖性过敏反应在 XID 小鼠中减弱。此外，重复使用半抗原和 IgE 产生引起的皮肤反应可能受到 Btk 的调节，因为这些反应在 XID 小鼠中增加。