Division of Microbiology, Biomedical Technology Wing, Sree Chitra Tirunal Institute for Medical Science and Technology, Poojappura P.O, Thiruvananthapuram, Kerala, India.
In Vitro Cell Dev Biol Anim. 2013 Apr;49(4):260-9. doi: 10.1007/s11626-013-9595-3. Epub 2013 Mar 19.
Tobacco induces oxidative stress in the alveolar epithelium and causes its damage. Retinoic acid (RA) has a cardinal role in alveolar cell growth, differentiation, and maturation. The aim of the study was to investigate the role of cell-cell interactions and whether RA could reverse the effect of tobacco extract on epithelial function as expressed by surfactant synthesis. For this, an in vitro model, which provides multiple cell type interactions, as seen in vivo, was used. We had used the major lung cell types, alveolar epithelial and mesenchymal cells represented by the cell lines A549 (human lung adenocarcinoma cell line), and human fetal lung fibroblast-1 (HFL-1) for developing the monoculture and co-culture systems and studied the effect of tobacco extract and retinoic acid. The effect of tobacco and retinoic acid both singly and in combination on proliferation and surfactant synthesis was analyzed. Retinoic acid induced proliferation and upregulated surfactant synthesis in monocultures and co-cultures. Tobacco extract at 100 μg/ml concentration decreased A549 proliferation and upregulated surfactant protein mRNA expression. In co-cultures treated with tobacco extract (100 μg/ml), retinoic acid (1 μM), regulated cell proliferation, and surfactant protein mRNA expression vis-à-vis the monoculture system. This clearly points to the fact that cell-cell interactions modulate the effect of additives or stimulants and help in assessing the in vivo combinatorial responses in vitro and that the retinoic acid effect is regenerative.
烟草会在肺泡上皮细胞中引起氧化应激，并导致其损伤。视黄酸（RA）在肺泡细胞的生长、分化和成熟中起着至关重要的作用。本研究旨在探讨细胞-细胞相互作用的作用，以及视黄酸是否可以逆转烟草提取物对上皮功能的影响，如表面活性剂合成的表达。为此，使用了一种体外模型，该模型提供了多种细胞类型的相互作用，如体内所见。我们使用了主要的肺细胞类型，即肺泡上皮细胞和间质细胞，分别由 A549（人肺腺癌细胞系）和人胎儿肺成纤维细胞-1（HFL-1）细胞系代表，用于开发单核和共培养系统，并研究了烟草提取物和视黄酸的作用。分析了烟草和视黄酸单独和联合对增殖和表面活性剂合成的影响。视黄酸在单核和共培养物中诱导增殖并上调表面活性剂合成。烟草提取物在 100μg/ml 浓度下降低 A549 增殖并上调表面蛋白 mRNA 表达。在经 100μg/ml 烟草提取物处理的共培养物中，视黄酸（1μM）调节细胞增殖和表面蛋白 mRNA 表达，与单核培养物系统相比。这清楚地表明细胞-细胞相互作用调节添加剂或刺激物的作用，并有助于评估体外体内组合反应，并且视黄酸的作用是再生性的。
