Involvement of intracellular caveolin‐1 distribution in the suppression of antigen‐induced mast cell activation by cationic liposomes
Involvement of intracellular caveolin‐1 distribution in the suppression of antigen‐induced mast cell activation by cationic liposomes
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细胞内caveolin-1分布参与阳离子脂质体抑制抗原诱导的肥大细胞活化
DOI：
10.1002/cbin.11297
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发表时间：
2020
影响因子：
3.9
通讯作者：
Furuno Tadahide
中科院分区：
文献类型：
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作者：
Inoh Yoshikazu;Tsuchiya Yuuki;Nakanishi Yokiko;Yokawa Satoru;Furuno Tadahide
阳离子脂质体通常被用作载体来有效地将外源基因导入靶细胞。在另一项功能中，我们最近发现结合在肥大细胞表面的阳离子脂质体以时间和剂量依赖的方式抑制高亲和力免疫球蛋白E受体的交联所引起的脱颗粒。这种抑制是通过抑制储存操作的钙内流来损害细胞内持续的钙离子浓度([钙]i)水平。进一步，我们揭示了[Ca~(2+)]i升高的机制是抑制磷脂酰肌醇3-激酶(PI3K)-Akt通路的激活。然而，阳离子脂质体如何抑制PI3K-Akt途径仍不清楚。在这里，我们重点研究了小窝的主要成分小窝蛋白-1，据报道它参与了各种细胞系中PI3K-Akt通路的激活。在这项研究中，我们发现小窝蛋白-1在肥大细胞激活后从细胞质转移到质膜上，并与PI3K的P85亚单位共定位，这似乎是PI3K活性所必需的。同时，阳离子脂质体抑制了小窝蛋白-1向质膜的移位，并抑制了小窝蛋白-1与PI3K P85在质膜上的共定位。这一发现为使用阳离子脂质体治疗过敏的开发提供了新的信息。
Cationic liposomes are commonly used as vectors to effectively introduce foreign genes into target cells. In another function, we recently showed that cationic liposomes bound to the mast cell surface suppress the degranulation induced by the cross‐linking of high‐affinity immunoglobulin E receptor in a time‐ and dose‐dependent manner. This suppression is mediated by the impairment of the sustained level of intracellular Ca2+concentration ([Ca2+]i) via the inhibition of store‐operated Ca2+entry. Further, we revealed that the mechanism underlying an impaired [Ca2+]iincrease is the inhibition of the activation of the phosphatidylinositol 3‐kinase (PI3K)‐Akt pathway. Yet, how cationic liposomes inhibit the PI3K‐Akt pathway is still unclear. Here, we focused on caveolin‐1, a major component of caveolae, which is reported to be involved in the activation of the PI3K‐Akt pathway in various cell lines. In this study, we showed that caveolin‐1 translocated from the cytoplasm to the plasma membrane after the activation of mast cells and colocalized with the p85 subunit of PI3K, which seemed to be essential for PI3K activity. Meanwhile, cationic liposomes suppressed the translocation of caveolin‐1 to the plasma membrane and the colocalization of caveolin‐1 with PI3K p85 also at the plasma membrane. This finding provides new information for the development of therapies using cationic liposomes against allergies.