Innate immune activation by inhaled lipopolysaccharide, independent of oxidative stress, exacerbates silica-induced pulmonary fibrosis in mice.
Innate immune activation by inhaled lipopolysaccharide, independent of oxidative stress, exacerbates silica-induced pulmonary fibrosis in mice.
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DOI：
10.1371/journal.pone.0040789
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Fattman CL
中科院分区：
文献类型：
--
作者：
Brass DM;Spencer JC;Li Z;Potts-Kant E;Reilly SM;Dunkel MK;Latoche JD;Auten RL;Hollingsworth JW;Fattman CL
肺纤维化急性加重的特点是肺功能迅速下降。可能导致急性加重的环境因素仍然知之甚少。我们以前已经证明，暴露在吸入性脂多糖(LPS)中会诱导与纤维化相关的基因表达。为了研究暴露于脂多糖是否会加剧肝纤维化，我们将雄性C57BL/6小鼠暴露在晶状二氧化硅或载体中，28天后再吸入脂多糖或生理盐水。我们观察到，与单独接受或单独接受二氧化硅的小鼠相比，同时接受二氧化硅和内毒素的小鼠有更多的总炎性细胞，更多的全肺灌洗液MCP-1，MIP-2，KC和IL-1β，更多的氧化应激证据和更多的肺总羟脯氨酸。用N-乙酰半胱氨酸阻断氧化应激可减轻全肺炎症，但对总肺羟脯氨酸无影响。这些观察结果表明，暴露于先天免疫刺激，如环境中的内毒素，可能通过独立于炎症和氧化应激的机制来加剧稳定型肺纤维化。
Acute exacerbations of pulmonary fibrosis are characterized by rapid decrements in lung function. Environmental factors that may contribute to acute exacerbations remain poorly understood. We have previously demonstrated that exposure to inhaled lipopolysaccharide (LPS) induces expression of genes associated with fibrosis. To address whether exposure to LPS could exacerbate fibrosis, we exposed male C57BL/6 mice to crystalline silica, or vehicle, followed 28 days later by LPS or saline inhalation. We observed that mice receiving both silica and LPS had significantly more total inflammatory cells, more whole lung lavage MCP-1, MIP-2, KC and IL-1β, more evidence of oxidative stress and more total lung hydroxyproline than mice receiving either LPS alone, or silica alone. Blocking oxidative stress with N-acetylcysteine attenuated whole lung inflammation but had no effect on total lung hydroxyproline. These observations suggest that exposure to innate immune stimuli, such as LPS in the environment, may exacerbate stable pulmonary fibrosis via mechanisms that are independent of inflammation and oxidative stress.
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DOI：
10.1164/rccm.200804-535oc
发表时间：
2009-01-15
影响因子：
24.7
作者：
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通讯作者：
Kleeberger, Steven R.