Silencing airway epithelial cell-derived hepcidin exacerbates sepsis induced acute lung injury.
Silencing airway epithelial cell-derived hepcidin exacerbates sepsis induced acute lung injury.
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DOI：
10.1186/s13054-014-0470-8
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发表时间：
2014-08-06
期刊：
影响因子：
--
通讯作者：
Fang XM
中科院分区：
文献类型：
--
作者：
Chen QX;Song SW;Chen QH;Zeng CL;Zheng X;Wang JL;Fang XM
气道上皮细胞产生抗菌肽是肺部感染和炎症先天免疫反应的重要组成部分。铁调素是一种β-防御素样抗菌肽，是一种主要的铁调节激素。铁调素主要由肝细胞产生，但也由其他细胞表达，如气道上皮细胞。然而，关于它在肺部感染和炎症性疾病中的作用还一无所知。因此，我们试图研究气道上皮细胞来源的铁调素在脓毒症诱导的急性肺损伤中的作用。通过盲肠结扎穿孔（CLP）手术由多种微生物脓毒症诱导急性肺损伤。将腺病毒介导的特异于小鼠hepcidin基因hepc 1的短发夹RNA和对照腺病毒注射到小鼠体内。在体内评估腺病毒介导的气道上皮细胞中铁调素的敲低。评估肺损伤和7天存活率。检测铁调素相关铁输出蛋白铁转运蛋白（ferroportin）的水平，评价肺泡巨噬细胞铁含量和功能。多菌性脓毒症气道上皮细胞铁调素水平上调。气道上皮细胞源性hepcidin基因敲低可加重脓毒症所致的肺损伤和肺部细菌感染，增加死亡率（Ad-shHepc 1组53.33%，Ad-shNeg组12.5%，P <0.05）。气道上皮细胞中铁调素的敲低也导致肺泡巨噬细胞中铁转运蛋白降解减少和细胞内铁含量降低。此外，来自气道上皮细胞来源的铁调素敲低小鼠的肺泡巨噬细胞显示出比来自对照小鼠的那些吞噬能力受损。气道上皮细胞源性铁调素在CLP诱导的急性肺损伤中起重要作用。气道上皮细胞源性铁调素敲低小鼠的严重肺损伤至少部分与细胞内铁水平和肺泡巨噬细胞功能的改变有关。
The production of antimicrobial peptides by airway epithelial cells is an important component of the innate immune response to pulmonary infection and inflammation. Hepcidin is a β-defensin-like antimicrobial peptide and acts as a principal iron regulatory hormone. Hepcidin is mostly produced by hepatocytes, but is also expressed by other cells, such as airway epithelial cells. However, nothing is known about its function in lung infections and inflammatory diseases. We therefore sought to investigate the role of airway epithelial cell-derived hepcidin in sepsis-induced acute lung injury. Acute lung injury was induced by polymicrobial sepsis via cecal ligation and puncture (CLP) surgery. Adenovirus-mediated short hairpin RNA specific for the mouse hepcidin gene hepc1 and control adenovirus were intratracheally injected into mice. The adenovirus-mediated knockdown of hepcidin in airway epithelial cells was evaluated in vivo. Lung injury and the seven-day survival rate were assessed. The levels of hepcidin-related iron export protein ferroportin were measured, and the iron content and function of alveolar macrophages were evaluated. The hepcidin level in airway epithelial cells was upregulated during polymicrobial sepsis. The knockdown of airway epithelial cell-derived hepcidin aggravated the polymicrobial sepsis-induced lung injury and pulmonary bacterial infection and increased mortality (53.33% in Ad-shHepc1-treated mice versus 12.5% in Ad-shNeg-treated mice, P <0.05). The knockdown of hepcidin in airway epithelial cells also led to reduced ferroportin degradation and a low intracellular iron content in alveolar macrophages. Moreover, alveolar macrophages form the airway epithelial cell-derived hepcidin knockdown mice showed impaired phagocytic ability than those from the control mice. Airway epithelial cell-derived hepcidin plays an important role in CLP-induced acute lung injury. The severe lung injury in the airway epithelial cell-derived hepcidin knockdown mice is at least partially related to the altered intracellular iron level and function of alveolar macrophages.
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影响因子：
25.7
作者：
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Penninger JM
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DOI：
10.1164/rccm.201211-1967oc
发表时间：
2013-07-15
影响因子：
24.7
作者：
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