Silica and Double-Stranded RNA Synergistically Induce Bronchial Epithelial Apoptosis and Airway Inflammation
Silica and Double-Stranded RNA Synergistically Induce Bronchial Epithelial Apoptosis and Airway Inflammation
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二氧化硅和双链 RNA 协同诱导支气管上皮细胞凋亡和气道炎症
DOI：
10.1165/rcmb.2013-0281oc
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发表时间：
2014
期刊：
影响因子：
--
通讯作者：
Matsuda A
中科院分区：
文献类型：
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作者：
Unno H;Futamura K;Morita H;Kojima R;Arae K;Nakae S;Ida H;Saito H;Matsumoto K;Matsuda A
火山灰和沙漠尘埃的主要矿物成分二氧化硅晶体（Silica crystals，silica）可激活吞噬细胞中的caspase-1激活炎性小体分泌IL-1β。虽然已知吸入含二氧化硅的粉尘可能通过炎性小体激活而加剧慢性呼吸道疾病，但其对支气管上皮细胞的直接影响仍不清楚。在这里，我们表明，二氧化硅和双链RNA（dsRNA）协同诱导caspase-9依赖的细胞凋亡，但不炎性小体激活，支气管上皮细胞。向小鼠鼻内给予二氧化硅和dsRNA协同增强气道中的中性粒细胞浸润，而支气管肺泡灌洗液中没有IL-1β释放。组织病理学分析显示，二氧化硅或dsRNA单独诱导轻微的气道炎症，而联合给药显着增强气道炎症和上皮损伤。这些新的发现表明，吸入含二氧化硅的粉尘可能会导致炎性小体非依赖性气道炎症，可能是通过破坏上皮屏障，特别是在病毒感染时。这些反应也可能参与吸入含硅粉尘引起的急性肺损伤。
Silica crystals (silica), which are the main mineral component of volcanic ash and desert dust, can activate the caspase-1–activating inflammasome in phagocytic cells to secrete IL-1β. Although inhalation of silica-containing dust is known to exacerbate chronic respiratory diseases, probably through inflammasome activation, its direct effects on bronchial epithelial cells remain unclear. Here, we show that silica and double-stranded RNA (dsRNA) synergistically induces caspase-9–dependent apoptosis, but not inflammasome activation, of bronchial epithelial cells. Intranasal administration of silica and dsRNA to mice synergistically enhanced neutrophil infiltration in the airway without IL-1β release in the bronchoalveolar lavage fluid. Histopathological analysis revealed that silica or dsRNA alone induced slight airway inflammation, whereas combined administration significantly enhanced airway inflammation and epithelial damage. These novel findings suggest that inhalation of silica-containing dust may cause inflammasome-independent airway inflammation, possibly by damaging the epithelial barrier, especially at the time of viral infection. These responses may also be involved in acute lung injury caused by inhaled silica-containing dust.