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4-羟基-2-(4-羟基苯乙基)异吲哚啉-1,3-二酮对卵清蛋白诱导的过敏性哮喘的抑制作用

Suppressive Effect of 4-Hydroxy-2-(4-Hydroxyphenethyl) Isoindoline-1,3-Dione on Ovalbumin-Induced Allergic Asthma.

作者信息

Huang Jin, Su Mingzhi, Lee Bo-Kyung, Kim Mee-Jeong, Jung Jee H, Im Dong-Soon

机构信息

Molecular Inflammation Research Center for Aging Intervention (MRCA) and College of Pharmacy, Pusan National University, Busan 46241, Republic of Korea.

出版信息

Biomol Ther (Seoul). 2018 Nov 1;26(6):539-545. doi: 10.4062/biomolther.2018.006.

Abstract

4-Hydroxy-2-(4-hydroxyphenethyl)isoindoline-1,3-dione (PD1) is a synthetic phthalimide derivative of a marine compound. PD1 has peroxisome proliferator-activated receptor (PPAR) γ agonistic and anti-inflammatory effects. This study aimed to investigate the effect of PD1 on allergic asthma using rat basophilic leukemia (RBL)-2H3 mast cells and an ovalbumin (OVA)-induced asthma mouse model. , PD1 suppressed β-hexosaminidase activity in RBL-2H3 cells. In the OVA-induced allergic asthma mouse model, increased inflammatory cells and elevated Th2 and Th1 cytokine levels were observed in bronchoalveolar lavage fluid (BALF) and lung tissue. PD1 administration decreased the numbers of inflammatory cells, especially eosinophils, and reduced the mRNA and protein levels of the Th2 cytokines including interleukin (IL)-4 and IL-13, in BALF and lung tissue. The severity of inflammation and mucin secretion in the lungs of PD1-treated mice was also less. These findings indicate that PD1 could be a potential compound for anti-allergic therapy.

摘要

4-羟基-2-(4-羟基苯乙基)异吲哚啉-1,3-二酮(PD1)是一种海洋化合物的合成邻苯二甲酰亚胺衍生物。PD1具有过氧化物酶体增殖物激活受体(PPAR)γ激动和抗炎作用。本研究旨在利用大鼠嗜碱性白血病(RBL)-2H3肥大细胞和卵清蛋白(OVA)诱导的哮喘小鼠模型研究PD1对过敏性哮喘的影响。PD1抑制了RBL-2H3细胞中的β-己糖胺酶活性。在OVA诱导的过敏性哮喘小鼠模型中,支气管肺泡灌洗液(BALF)和肺组织中观察到炎症细胞增多以及Th2和Th1细胞因子水平升高。给予PD1可减少炎症细胞数量,尤其是嗜酸性粒细胞,并降低BALF和肺组织中包括白细胞介素(IL)-4和IL-13在内的Th2细胞因子的mRNA和蛋白质水平。PD1治疗小鼠肺部的炎症严重程度和粘蛋白分泌也较低。这些发现表明PD1可能是一种潜在的抗过敏治疗化合物。

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