Air pollution-associated fly ash particles induce fibrotic mechanisms in primary fibroblasts
Air pollution-associated fly ash particles induce fibrotic mechanisms in primary fibroblasts
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DOI：
10.1515/bc.2006.177
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发表时间：
2006-10-01
影响因子：
3.7
通讯作者：
Simm, Andreas
中科院分区：
文献类型：
--
作者：
Gursinsky, Torsten;Ruhs, Stefanie;Simm, Andreas
空气污染与各种呼吸道和心血管疾病有关，包括纤维化。为了了解这一观察结果背后可能的分子机制，我们研究了颗粒物质对细胞外基质的关键调节因子--原代成纤维细胞的影响。在实验垃圾焚烧炉收集的飞灰被用作模型颗粒细和超细污染成分。从成年雄性Wistar大鼠心脏分离的成纤维细胞与粉煤灰的短暂治疗触发细胞内活性氧簇（ROS）的立即形成。使用磷酸化特异性抗体，我们观察到p38 MAP激酶，p44/42 MAP激酶（ERK 1/2）和p70（S6）激酶的激活。长时间与粉煤灰一起孵育增加了胶原1和TGF-β 1的表达，但降低了MMP 9和TNF-α的mRNA水平。高浓度粉煤灰对细胞增殖有抑制作用。观察到用粉煤灰长期处理培养的成纤维细胞后，各种细胞蛋白的晚期糖基化终产物（AGE）修饰水平增加。我们的研究结果表明，燃烧产生的颗粒直接激活成纤维细胞是一种可能导致颗粒空气污染对健康不利影响的机制。
Air pollution is associated with a variety of respiratory and cardiovascular disorders, including fibrosis. To understand the possible molecular mechanisms underlying this observation, we examined the effect of particulate matter on primary fibroblasts, the key regulators of the extracellular matrix. Fly ash collected in an experimental waste incinerator was used as model particles for fine and ultrafine pollution components. Brief treatment of fibroblasts isolated from adult male Wistar rat hearts with fly ash triggered the immediate formation of intracellular reactive oxygen species (ROS). Using phospho-specific antibodies we observed activation of p38 MAP kinase, p44/42 MAP kinase (ERK1/2) and p70(S6) kinase. Prolonged incubation with fly ash increased the expression of collagen 1 and TGF-beta 1, but decreased mRNA levels of MMP9 and TNF-alpha. Cell proliferation was inhibited at high concentrations of fly ash. An increase in the level of advanced glycation endproduct (AGE) modification of various cellular proteins after long-term treatment of cultured fibroblasts with fly ash was observed. The results of our study demonstrate that direct activation of fibroblasts by combustion-derived particles is a mechanism that may contribute to the adverse health effects of particulate air pollution.