Regulation of cytokine production through the receptors for lysophospholipid in mast cells

通过肥大细胞中溶血磷脂受体调节细胞因子的产生

基本信息

批准号：
11670434
负责人：
ISHIZUKA Tamotsu
金额：
$ 2.3万
依托单位：
Gunma University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1999
资助国家：
日本
起止时间：
1999 至 2000
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11670434/
关键词：
Mast Cell Cell Migration Cytokine p38 MAP Kinase Rho-kinase MAPKAP kinase Protein Kinase Cμ Antigen 肥満細胞サイトカイン protein kinase C MAP Kinase

项目摘要

We found that mast cells express receptors for lysophspholipid. However, we cannot find the evidence that lysophospholipid modulates IgE Fc receptor (FcεRI)-mediated cytokine production in mast cells. We expects one of protein kinase C (PKC) members, PKCμ, is involved in FcεRI-mediated C-Jun amino-terminal kinase (JNK) activation and cytokine production in mast cells because only PKC inhibitors which inhibit PKCμ abolish FcεRI-mediated JNK activation but not those which cannot inhibit PKCμ. Although an accumulation of mast cells within the epithelial layer of the mucosa is observed in patients with allergic rhinitis and bronchial asthma, the responsible chemotactic factors are undefined. We investigated whether mast cells sensitized with antigen-specific IgE migrate toward the antigen or not. MC/9 mast cells sensitized with anti-dinitrophenyl (DNP) IgE migrated toward DNP conjugated human serum albumin (DNP-HSA). This migration was directional, and the degree of migration was stronger … More than that of stem cell factor (SCF)-induced migration. Mouse bone marrow-derived cultured mast cells (BMMC) also migrated toward the antigen. The high-affinity IgE Fc receptor (FcεRI)-mediated migration was significantly inhibited by pretreatment of-the cells with Y-27632, a Rho-associated coiled-coil forming protein kinase (ROCK) inhibitor, or SB 203580, a p38 MAP kinase (p38 MAPK) inhibitor. Both p38 MAPK and MAPKAP kinase 2 were activated following aggregation of FcεRI, and activation of MAPKAP kinase 2 was almost completely inhibited by 10μM SB203580. Partial inhibition of MAPKAP kinase 2 by pretreatment with wortmannin or a low concentration of SB203580 was not enough to block mast cell migration. On the other hand, Y-27632 did not affect the activation of MAPKAP kinase 2. These results indicate that antigen works not only as a stimulant for allergic mediators from IgE-sensitized mast cells but also as a chemotactic factor for mast cells. Both p38 MAPK activation and Rho-dependent activation of ROCK may be required for FcεRI-mediated cell migration. Less

我们发现肥大细胞表达用于溶血球体的受体。但是，我们找不到证据表明溶物磷脂调节肥大细胞中IgE FC受体（FCεRI）介导的细胞因子的产生。 We expect one of protein kinase C (PKC) members, PKCμ, is involved in FcεRI-mediated C-Jun amino-terminal kinase (JNK) activation and cytokine production in mast cells because only PKC inhibitors which inhibit PKCμ abolish FcεRI-mediated JNK activation but not those which cannot inhibit PKCμ.尽管在过敏性鼻炎和支气管哮喘患者中观察到肥大细胞在粘膜上皮层中的积累，但负责的趋化因子是不确定的。我们研究了对抗原特异性IgE敏感的肥大细胞是否向抗原迁移。 MC/9肥大细胞对抗二硝基苯基（DNP）IgE敏感，迁移到DNP共轭人血清专辑（DNP-HSA）。这种迁移是指向的，迁移程度更强……不仅仅是干细胞因子（SCF）诱导的迁移的迁移程度。小鼠骨髓衍生的培养肥大细胞（BMMC）也向抗原迁移。高亲和力IgE FC受体（FCεRI）介导的迁移被用Y-27632预处理（一种与RHO相关的盘绕螺旋形成蛋白激酶（ROCK）抑制剂或SB 203580，P38 Mapk Kinase（p38 Mapk kinase（P38 Map Map）Inbimk）的细胞（Y-27632预处理）。在FCεRI聚集后，p38 MAPK和MAPKAP激酶2均激活，MAPKAP激酶2的激活几乎被10μMSB203580完全抑制。通过用伤口曼宁或低浓度的SB203580预处理MAPKAP激酶2的部分抑制不足以阻断肥大细胞迁移。另一方面，Y-27632不影响MAPKAP激酶2的激活。这些结果表明，抗原不仅可以作为来自IgE敏感肥大细胞的过敏介质的刺激性，而且还可以作为肥大细胞的趋化因子。 FcεRI介导的细胞迁移可能需要P38 MAPK激活和岩石的Rho依赖性激活。较少的