Bastan Reza, Eskandari Nahid, J Ardakani Hamidrez, T Peachell Peter
a Department of Human Vaccines , Razi Serum and Vaccine Research Institute , Karaj , Iran.
b Department of Immunology , Applied Physiology Research Center, Isfahan University of Medical Sciences , Isfahan , Iran.
J Immunotoxicol. 2017 Dec;14(1):60-65. doi: 10.1080/1547691X.2016.1259277. Epub 2017 Jan 16.
As part of the intracellular processes leading to mast cell and basophil activation, phosphorylation of key substrates is likely to be important. These processes, mediated by phosphatases, are responsible for regulating phosphorylation. The aim of the present study was to determine effects fostriecin - a selective inhibitor of PP2A (protein phosphatase-2) - on β-adrenoceptor-driven responses in human mast cells. Here, the effects of fostriecin (PP inhibitors) on the inhibition of histamine release from HLMC, on β-adrenoceptor-driven responses in mast cells and on desensitization were investigated. Long-term incubation (24 h) of mast cells with fostriecin (10 M) resulted in a significant (p < 0.001) reduction in the maximal response (from 41.2 [± 3.0] to 29.9 [± 4.2] %) to salbutamol following fostriecin treatment. The results showed that fostriecin pretreatment significantly attenuated the inhibitory effects of salbutamol. Overall, the present study suggested that PP2A has an important role in regulating mast cell β-adrenoceptors.
作为导致肥大细胞和嗜碱性粒细胞活化的细胞内过程的一部分,关键底物的磷酸化可能很重要。这些由磷酸酶介导的过程负责调节磷酸化。本研究的目的是确定福斯曲星(一种PP2A(蛋白磷酸酶2)的选择性抑制剂)对人肥大细胞中β-肾上腺素能受体驱动反应的影响。在此,研究了福斯曲星(PP抑制剂)对抑制HLMC中组胺释放、对肥大细胞中β-肾上腺素能受体驱动反应以及对脱敏的影响。用福斯曲星(10 μM)对肥大细胞进行长期孵育(24小时)导致福斯曲星处理后对沙丁胺醇的最大反应显著降低(p < 0.001)(从41.2 [±3.0]%降至29.9 [±4.2]%)。结果表明,福斯曲星预处理显著减弱了沙丁胺醇的抑制作用。总体而言,本研究表明PP2A在调节肥大细胞β-肾上腺素能受体中起重要作用。