Sardarian Ahmadreza, Andisheh Tadbir Azadeh, Zal Fatemeh, Amini Fatemeh, Jafarian Aida, Khademi Fatemeh, Mostafavi-Pour Zohreh
Department of Orthodontics, Orthodontic Research Center, School of Dentistry, Shiraz University of Medical Sciences , Shiraz , Iran .
Toxicol Mech Methods. 2015 Feb;25(2):98-104. doi: 10.3109/15376516.2014.990595. Epub 2015 Jan 22.
Cyclosporine A (CsA) is an immunosuppressive agent administered to transplant patients. A well-known reported oral side effect of CsA consumption is gingival overgrowth (GO). Changes in the expression of integrins occurring in the gingiva following CsA treatment have been reported but these reports are mainly concerned with the connective tissue of the gingiva. In this study we targeted the alterations in the oral epithelium using KB cells, an oral epithelial cell line.
Cultured oral epithelial cells were treated with increasing concentrations of CsA (0.1, 1 and 10 µg/mL) and the molecular changes involving antioxidant enzymes [glutathione peroxidase (GPx) and glutathione reductase (GR)] and the level of reactive oxygen species (ROS) were measured. Quantitative real-time PCR was used to assess the expression of selected integrins (α2, α5 and β1).
At CsA concentration above 0.1 µg/mL GPx demonstrated an increase in activity while GR activity and the level of reduced glutathione were diminished (p < 0.05). α5 and β1 integrin were downregulated at all treatment concentrations of CsA while α2 integrin presented this effect at concentrations above 1 µg/mL (p < 0.05).
The results suggest a possible role for oxidative stress and the altered expression of integrins in the pathology of CsA-induced gingival overgrowth.
环孢素A(CsA)是一种用于移植患者的免疫抑制剂。CsA口服的一个众所周知的副作用是牙龈增生(GO)。已有报道称CsA治疗后牙龈中整合素表达发生变化,但这些报道主要关注牙龈的结缔组织。在本研究中,我们使用口腔上皮细胞系KB细胞来研究口腔上皮的变化。
用浓度递增的CsA(0.1、1和10μg/mL)处理培养的口腔上皮细胞,测量涉及抗氧化酶[谷胱甘肽过氧化物酶(GPx)和谷胱甘肽还原酶(GR)]的分子变化以及活性氧(ROS)水平。采用定量实时PCR评估所选整合素(α2、α5和β1)的表达。
当CsA浓度高于0.1μg/mL时,GPx活性增加,而GR活性和还原型谷胱甘肽水平降低(p<0.05)。在所有CsA处理浓度下,α5和β1整合素均下调,而α2整合素在浓度高于1μg/mL时出现这种效应(p<0.05)。
结果表明氧化应激和整合素表达改变在CsA诱导的牙龈增生病理过程中可能起作用。