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Bruton的酪氨酸激酶（BTK）在过敏反应中的作用，我们研究了与CBA/N（XID）小鼠和CBA/JXCBA/N F1雄性小鼠相比，与其对照小鼠相比，CBA/JXCBA/N F1雄性小鼠的某些实验性过敏反应与CBA/J和CBA/J和CBA/JXCBA/N F1雌性小鼠相比。此外，还采用反义寡核苷酸来检查BTK在培养的人桅杆细胞中释放中介质的作用。与雌性小鼠相比，CBA/JXCBA/N F1雄性小鼠在CBA/JXCBA/N F1雄性小鼠中降低了二硝基氟苯诱导的三个阶段。与CBA/J小鼠相比，卵蛋白免疫诱导的CBA/N小鼠的IgM产生显然很低，而CBA/N小鼠的IgE产生显然很高。 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.在本研究中，我们在刺激前用反义寡核苷酸处理了一周。组胺释放和GM-CSF的产生不受治疗的影响。在当前的实验条件下，反义寡核苷酸可能不会有效地引入肥大细胞。我们需要使用不同的实验条件进行其他实验。这些结果和去年获得的先前数据表明，由于肥大细胞的激活不足，XID小鼠的IgE依赖性过敏反应减弱。 BTK可能不会促进巨噬细胞谱系细胞的激活。此外，由于XID小鼠中这些反应的增加，由于反复施用和IgE产生的重复施用和IgE产生可能会调节皮肤反应。