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Microcystin-LR induced oxidative stress, inflammation, and apoptosis in alveolar type II epithelial cells of ICR mice in vitro.

微囊藻毒素-LR 在体外诱导 ICR 小鼠肺泡 ⅱ 型上皮细胞的氧化应激、炎症和凋亡。

  • 影响因子:2.45
  • DOI:10.1016/j.toxicon.2019.12.152
  • 作者列表:"Zhong S","Liu Y","Wang F","Wu Z","Zhao S
  • 发表时间:2020-01-30

:Previous studies have shown that microcystin-LR (MC-LR) produced by toxic cyanobacterial blooms could inflict damage to the lung. However, the mechanisms underlying MC-induced pulmonary toxicity are not fully described. In this study, the primary' fetal alveolar type II epithelial cells (AEC II) from ICR mice, which are involved in formation of bioactive component of pulmonary epithelium and secretion of pulmonary surfactants, were exposed to MC-LR at different concentrations (0, 0.625, 1.25, 2.5, 5, 10, 20 μg/mL) for different time (12, 24, 36 h). Results showed that the viabilities of AEC II exposed to 10 and 20 μg MC-LR/mL were significantly decreased compared with the control group. Furthermore, MC-LR exposure resulted in overproduction of reactive oxygen species (ROS) and induced a significant reduction in superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px). Expressions of apoptosis-related proteins including bax, cyt-c, and caspase-9 were significantly up-regulated by exposure to 2.5, 5, 10, or 20 μg MC-LR/mL. When exposed to 5, 10, or 20 μg MC-LR/mL, expressions of proteins involved in inflammatory, p-65 and iNOS were significantly greater than those of the controls. In conclusion, inflammation and apoptosis might be responsible for MC-LR-induced pulmonary injury.


: 以前的研究表明,有毒蓝藻水华产生的微囊藻毒素-LR (MC-LR) 会对肺造成损伤。然而,MC 诱导肺毒性的机制尚未完全描述。本研究主要从 ICR 小鼠的胎儿肺泡 ⅱ 型上皮细胞 (AEC ⅱ) 中筛选出参与肺上皮生物活性成分形成和分泌肺表面活性剂的细胞, 暴露于不同浓度 (0 、 0.625 、 1.25 、 2.5 、 5 、 10 、 20 μ g/mL) 的 MC-LR对于不同的时间 (12 、 24 、 36 h)。结果表明,与对照组相比,10 和 20 μ g MC-LR/mL 染毒组 AEC ⅱ 的活力显著降低。此外,MC-LR 暴露导致活性氧 (ROS) 过量产生,并诱导超氧化物歧化酶 (SOD) 和谷胱甘肽过氧化物酶 (GSH-Px) 显著降低。2.5 、 5 、 10 或 20 μ g MC-LR/mL 可显著上调细胞凋亡相关蛋白 bax 、 cyt-c 和 caspase-9 的表达。当暴露于 5 、 10 或 20 μ g MC-LR/mL 时,参与炎症、 p-65 和 iNOS 的蛋白表达显著高于对照组。总之,炎症和细胞凋亡可能是 MC-LR 诱导的肺损伤的原因。



作者列表:["De Cunto G","Brancaleone V","Riemma MA","Cerqua I","Vellecco V","Spaziano G","Cavarra E","Bartalesi B","D'Agostino B","Lungarella G","Cirino G","Lucattelli M","Roviezzo F"]

METHODS:BACKGROUND AND PURPOSE:A critical role for sphingosine kinase/sphingosine-1-phosphate (S1P) pathway in the control of airway function has been demonstrated in respiratory diseases. Here, we address S1P contribution in a mouse model of mild chronic obstructive pulmonary disease (COPD). EXPERIMENTAL APPROACH:C57BL/6J mice have been exposed to room air or cigarette smoke up to 11 months and killed at different time points. Functional and molecular studies have been performed. KEY RESULTS:Cigarette smoke caused emphysematous changes throughout the lung parenchyma coupled to a progressive collagen deposition in both peribronchiolar and peribronchial areas. The high and low airways showed an increased reactivity to cholinergic stimulation and α-smooth muscle actin overexpression. Similarly, an increase in airway reactivity and lung resistances following S1P challenge occurred in smoking mice. A high expression of S1P, Sph-K2 , and S1P receptors (S1P2 and S1P3 ) has been detected in the lung of smoking mice. Sphingosine kinases inhibition reversed the increased cholinergic response in airways of smoking mice. CONCLUSIONS AND IMPLICATIONS:S1P signalling up-regulation follows the disease progression in smoking mice and is involved in the development of airway hyperresponsiveness. Our study defines a therapeutic potential for S1P inhibitors in management of airways hyperresponsiveness associated to emphysema in smokers with both asthma and COPD.

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作者列表:["Bernstein DM","Toth B","Rogers RA","Kling DE","Kunzendorf P","Phillips JI","Ernst H"]

METHODS::The interim results from this 90-day multi-dose, inhalation toxicology study with life-time post-exposure observation has shown an important fundamental difference in persistence and pathological response in the lung between brake dust derived from brake-pads manufactured with chrysotile, TiO2 or chrysotile alone in comparison to the amphiboles, crocidolite and amosite asbestos. In the brake dust exposure groups no significant pathological response was observed at any time. Slight macrophage accumulation of particles was noted. Wagner-scores, were from 1 to 2 (1 = air-control group) and were similar to the TiO2 group. Chrysotile being biodegradable, shows a weakening of its matrix and breaking into short fibers & particles that can be cleared by alveolar macrophages and continued dissolution. In the chrysotile exposure groups, particle laden macrophage accumulation was noted leading to a slight interstitial inflammatory response (Wagner-score 1-3). There was no peribronchiolar inflammation and occasional very slight interstitial fibrosis. The histopathology and the confocal analyses clearly differentiate the pathological response from amphibole asbestos, crocidolite and amosite, compared to that from the brake dust and chrysotile. Both crocidolite and amosite induced persistent inflammation, microgranulomas, and fibrosis (Wagner-scores 4), which persisted through the post exposure period. The confocal microscopy of the lung and snap-frozen chestwalls quantified the extensive inflammatory response and collagen development in the lung and on the visceral and parietal surfaces. The interim results reported here, provide a clear basis for differentiating the effects from brake dust exposure from those following amphibole asbestos exposure. The subsequent results through life-time post-exposure will follow.

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作者列表:["Zaragosi LE","Deprez M","Barbry P"]

METHODS::The respiratory tract is lined by a pseudo-stratified epithelium from the nose to terminal bronchioles. This first line of defense of the lung against external stress includes five main cell types: basal, suprabasal, club, goblet and multiciliated cells, as well as rare cells such as ionocytes, neuroendocrine and tuft/brush cells. At homeostasis, this epithelium self-renews at low rate but is able of fast regeneration upon damage. Airway epithelial cell lineages during regeneration have been investigated in the mouse by genetic labeling, mainly after injuring the epithelium with noxious agents. From these approaches, basal cells have been identified as progenitors of club, goblet and multiciliated cells, but also of ionocytes and neuroendocrine cells. Single-cell RNA sequencing, coupled to lineage inference algorithms, has independently allowed the establishment of comprehensive pictures of cell lineage relationships in both mouse and human. In line with genetic tracing experiments in mouse trachea, studies using single-cell RNA sequencing (RNAseq) have shown that basal cells first differentiate into club cells, which in turn mature into goblet cells or differentiate into multiciliated cells. In the human airway epithelium, single-cell RNAseq has identified novel intermediate populations such as deuterosomal cells, 'hybrid' mucous-multiciliated cells and progenitors of rare cells. Novel differentiation dynamics, such as a transition from goblet to multiciliated cells have also been discovered. The future of cell lineage relationships in the respiratory tract now resides in the combination of genetic labeling approaches with single-cell RNAseq to establish, in a definitive manner, the hallmarks of cellular lineages in normal and pathological situations.

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