Protein Disulfide Isomerases Regulate IgE-Mediated Mast Cell Responses and Their Inhibition Confers Protective Effects During Food Allergy.
Protein Disulfide Isomerases Regulate IgE-Mediated Mast Cell Responses and Their Inhibition Confers Protective Effects During Food Allergy.
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DOI：
10.3389/fimmu.2020.606837
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发表时间：
2020
影响因子：
7.3
通讯作者：
Mathias CB
中科院分区：
文献类型：
--
作者：
Krajewski D;Polukort SH;Gelzinis J;Rovatti J;Kaczenski E;Galinski C;Pantos M;Shah NN;Schneider SS;Kennedy DR;Mathias CB
巯基异构酶，蛋白质二硫键异构酶（PDI），在蛋白质折叠过程中发挥重要的细胞内作用，维持细胞功能和活力。最近的研究表明，细胞外表面PDI在增强细胞活化和促进其功能方面具有新的作用。此外，许多食物来源的物质已被证明可以调节细胞PDI活性并改变疾病进展。我们假设PDI在肥大细胞介导的过敏反应中可能具有类似的作用，并研究了其对IgE诱导的肥大细胞活性在细胞培养和食物过敏中的影响。肥大细胞通过IgE和抗原活化，并评估PDI抑制对肥大细胞活化的影响。在卵清蛋白诱导的食物过敏模型中，通过用不可逆的PDI抑制剂PACMA-31处理小鼠来检查体内PDI阻断的效果。使用包括姜黄素和槲皮素-3-芸香糖苷（芸香苷）的各种膳食化合物来研究膳食PDI调节剂的作用。PDI的表达，观察到静止的肥大细胞表面，细胞内，并在过敏性小鼠的肠道。此外，在IgE和抗原活化期间，在肥大细胞膜上观察到细胞外PDI的分泌增强。胰岛素比浊测定表明，姜黄素是一种有效的PDI抑制剂，用姜黄素或已建立的PDI抑制剂如杆菌肽、芦丁或PACMA-31预处理肥大细胞，导致IgE介导的活化和各种细胞因子的分泌受到抑制。这伴随着肥大细胞增殖、FcεRI表达和肥大细胞脱粒的减少。类似地，用PACMA-31治疗过敏性BALB/c小鼠减弱了食物过敏的发展，导致过敏性腹泻减少、肥大细胞活化和肠肥大细胞减少。TH 2特异性细胞因子的产生也受到抑制。我们的观察结果表明，PDI催化活性是必不可少的调节肥大细胞活化，它的封锁可能有利于过敏性炎症患者。
The thiol isomerase, protein disulfide isomerase (PDI), plays important intracellular roles during protein folding, maintaining cellular function and viability. Recent studies suggest novel roles for extracellular cell surface PDI in enhancing cellular activation and promoting their function. Moreover, a number of food-derived substances have been shown to regulate cellular PDI activity and alter disease progression. We hypothesized that PDI may have similar roles during mast cell-mediated allergic responses and examined its effects on IgE-induced mast cell activity during cell culture and food allergy. Mast cells were activated via IgE and antigen and the effects of PDI inhibition on mast cell activation were assessed. The effects of PDI blockade in vivo were examined by treating mice with the irreversible PDI inhibitor, PACMA-31, in an ovalbumin-induced model of food allergy. The role of dietary PDI modulators was investigated using various dietary compounds including curcumin and quercetin-3-rutinoside (rutin). PDI expression was observed on resting mast cell surfaces, intracellularly, and in the intestines of allergic mice. Furthermore, enhanced secretion of extracellular PDI was observed on mast cell membranes during IgE and antigen activation. Insulin turbidimetric assays demonstrated that curcumin is a potent PDI inhibitor and pre-treatment of mast cells with curcumin or established PDI inhibitors such as bacitracin, rutin or PACMA-31, resulted in the suppression of IgE-mediated activation and the secretion of various cytokines. This was accompanied by decreased mast cell proliferation, FcεRI expression, and mast cell degranulation. Similarly, treatment of allergic BALB/c mice with PACMA-31 attenuated the development of food allergy resulting in decreased allergic diarrhea, mast cell activation, and fewer intestinal mast cells. The production of TH2-specific cytokines was also suppressed. Our observations suggest that PDI catalytic activity is essential in the regulation of mast cell activation, and that its blockade may benefit patients with allergic inflammation.
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DOI：
10.1161/atvbaha.114.303410
发表时间：
2015-01
期刊：
Arteriosclerosis, thrombosis, and vascular biology
影响因子：
--
作者：
Flaumenhaft R;Furie B;Zwicker JI
通讯作者：
Zwicker JI
影响因子：
6.5
作者：
CHEN, K;DETWILER, TC;ESSEX, DW
通讯作者：
ESSEX, DW
影响因子：
6.4
作者：
Chen, SS;Gong, J;Mohammed, U
通讯作者：
Mohammed, U
影响因子：
15.9
作者：
Brandt, EB;Strait, RT;Rothenberg, ME
通讯作者：
Rothenberg, ME
影响因子：
4.8
作者：
Delom, F;Mallett, B;Lejeune, PJ
通讯作者：
Lejeune, PJ