Benediktsdottir Berglind Eva, Baldursson Olafur, Gudjonsson Thorarinn, Tønnesen Hanne Hjorth, Masson Mar
Faculty of Pharmaceutical Sciences, School of Health Sciences, University of Iceland, Hofsvallagata 53, IS-107 Reykjavik, Iceland.
Department of Pulmonary Medicine, Landspitali-The National University Hospital of Iceland, Eiríksgata 5, IS-101 Reykjavík, Iceland.
Biochem Biophys Rep. 2015 Nov 10;4:405-410. doi: 10.1016/j.bbrep.2015.11.004. eCollection 2015 Dec.
The phytochemical curcumin may improve translocation of the cystic fibrosis transmembrane regulatory (CFTR) protein in lung epithelium and therefore be helpful in the treatment of cystic fibrosis (CF) symptoms. However, previous studies often use commercial curcumin that is a combination of curcumin, demethoxycurcumin and bisdemethoxycurcumin which could affect the investigated cells differently. In the present study, we investigated the potential difference between curcumin, bisdemethoxycurcumin and dimethoxycurcumin on the epithelial tight junction complex, in the bronchial epithelial cell line VA10, by measuring transepithelial electrical resistance (TER), immunofluorescence and western blotting of tight junction proteins. The curcuminoids were complexed with hydroxypropyl-γ-cyclodextrin for increased solubility and stability. Curcumin (10 µg/ml) increased the TER significantly after 24 h of treatment while four times higher concentration of bisdemethoxycurcumin was required to obtain similar increase in TER as curcumin. Interestingly, dimethoxycurcumin did not increase TER. Curcumin clearly affected the F-actin structures both apically and basolaterally. These results begin to define possible effects of curcuminoids on healthy bronchial epithelia and shows that difference in the phenyl moiety structure of the curcuminoids influences the paracellular epithelial integrity.
植物化学物质姜黄素可能会改善肺上皮细胞中囊性纤维化跨膜调节蛋白（CFTR）的转运，因此有助于治疗囊性纤维化（CF）症状。然而，以往的研究通常使用商业姜黄素，它是姜黄素、去甲氧基姜黄素和双去甲氧基姜黄素的混合物，可能会对被研究细胞产生不同影响。在本研究中，我们通过测量跨上皮电阻（TER）、紧密连接蛋白的免疫荧光和蛋白质印迹，研究了姜黄素、双去甲氧基姜黄素和二甲氧基姜黄素对支气管上皮细胞系VA10上皮紧密连接复合体的潜在差异。姜黄素类化合物与羟丙基-γ-环糊精复合以提高溶解度和稳定性。处理24小时后，姜黄素（10μg/ml）显著增加了TER，而双去甲氧基姜黄素需要四倍于姜黄素的浓度才能获得类似的TER增加。有趣的是，二甲氧基姜黄素并未增加TER。姜黄素明显影响了顶端和基底外侧的F-肌动蛋白结构。这些结果开始明确姜黄素类化合物对健康支气管上皮细胞的可能作用，并表明姜黄素类化合物苯部分结构的差异会影响上皮细胞旁的完整性。
