Jaspers I, Zhang W, Brighton L E, Carson J L, Styblo M, Beck M A
Center for Environmental Medicine, Asthma, and Lung Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Free Radic Biol Med. 2007 Jun 15;42(12):1826-37. doi: 10.1016/j.freeradbiomed.2007.03.017. Epub 2007 Mar 24.
It is unknown whether nutritional deficiencies affect the morphology and function of structural cells, such as epithelial cells, and modify the susceptibility to viral infections. We developed an in vitro system of differentiated human bronchial epithelial cells (BEC) grown either under selenium-adequate (Se+) or selenium-deficient (Se-) conditions, to determine whether selenium deficiency impairs host defense responses at the level of the epithelium. Se- BECs had normal SOD activity, but decreased activity of the selenium-dependent enzyme GPX1. Interestingly, catalase activity was also decreased in Se- BECs. Both Se- and Se+ BECs differentiated into a mucociliary epithelium; however, Se- BEC demonstrated increased mucus production and increased Muc5AC mRNA levels. This effect was also seen in Se+ BEC treated with 3-aminotriazole, an inhibitor of catalase activity, suggesting an association between catalase activity and mucus production. Both Se- and Se+ were infected with influenza A/Bangkok/1/79 and examined 24 h postinfection. Influenza-induced IL-6 production was greater while influenza-induced IP-10 production was lower in Se- BECs. In addition, influenza-induced apoptosis was greater in Se- BEC as compared to the Se+ BECs. These data demonstrate that selenium deficiency has a significant impact on the morphology and influenza-induced host defense responses in human airway epithelial cells.
营养缺乏是否会影响结构细胞(如上皮细胞)的形态和功能,并改变对病毒感染的易感性尚不清楚。我们建立了一个体外分化人支气管上皮细胞(BEC)系统,该细胞在硒充足(Se+)或硒缺乏(Se-)条件下生长,以确定硒缺乏是否会在上皮水平损害宿主防御反应。Se- BEC具有正常的超氧化物歧化酶(SOD)活性,但硒依赖性酶谷胱甘肽过氧化物酶1(GPX1)的活性降低。有趣的是,Se- BEC中的过氧化氢酶活性也降低了。Se-和Se+ BEC均分化为黏液纤毛上皮;然而,Se- BEC显示黏液分泌增加且黏蛋白5AC(Muc5AC)mRNA水平升高。在用过氧化氢酶活性抑制剂3-氨基三唑处理的Se+ BEC中也观察到了这种效应,这表明过氧化氢酶活性与黏液分泌之间存在关联。Se-和Se+ BEC均感染甲型流感病毒/曼谷/1/79,并在感染后24小时进行检测。在Se- BEC中,流感诱导的白细胞介素-6(IL-6)产生更多,而流感诱导的干扰素诱导蛋白10(IP-10)产生更少。此外,与Se+ BEC相比,Se- BEC中流感诱导的细胞凋亡更多。这些数据表明,硒缺乏对人气道上皮细胞的形态和流感诱导的宿主防御反应有重大影响。