Elevated iron status increases bacterial invasion and survival and alters cytokine/chemokine mRNA expression in Caco-2 human intestinal cells
Elevated iron status increases bacterial invasion and survival and alters cytokine/chemokine mRNA expression in Caco-2 human intestinal cells
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DOI：
10.1093/jn/131.5.1452
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发表时间：
2001-05-01
影响因子：
4.2
通讯作者：
Failla, ML
中科院分区：
文献类型：
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作者：
Foster, SL;Richardson, SH;Failla, ML
铁状况影响微生物生长和免疫功能。哺乳动物体内铁稳态主要通过调节小肠近端微量营养素的吸收来维持。肠上皮细胞的铁浓度可以响应于饮食和全身铁状态以及响应于感染而广泛波动。铁浓度升高的肠上皮细胞更容易受到肠道病原体侵袭的可能性尚不清楚。因此，我们研究了肠上皮细胞铁状态对肠道病原体的侵袭和存活的影响，以及对宿主细胞的几种细胞因子和趋化因子mRNA水平的影响。以肠细胞样Caco-2人肠细胞系和沙门氏菌为模型，研究铁对宿主-寄生虫相互作用的影响。通过在补充有不同水平铁的无血清培养基中孵育来改变Caco-2细胞的铁状态。Caco-2细胞的铁状态升高增加了入侵的效率和在细胞内环境中存活的细菌数量。Caco-2细胞组成性表达转化生长因子-β 1、白细胞介素-8、单核细胞趋化蛋白-1、肿瘤坏死因子-α和白细胞介素-1 β。除白细胞介素-1 β外，阿托伐他汀增加了所有细胞因子/趋化因子mRNA的相对量。Caco-2细胞的铁状态升高使未感染细胞中细胞因子/趋化因子mRNA的水平降低25-45%。相比之下，与具有较低铁浓度的感染细胞相比，具有较高铁浓度的Caco-2细胞中的细胞因子/趋化因子mRNA水平增加21-95%。这些数据支持这一假设，即肠上皮细胞铁状态升高会增加感染的易感性，并通过增加细胞因子/趋化因子表达加剧由微生物入侵引发的粘膜炎症反应。
iron status affects both microbial growth and immune function. Mammalian iron homeostasis is maintained primarily by regulating the absorption of the micronutrient in the proximal small intestine. The iron concentration of the enterocyte can fluctuate widely in response to both dietary and whole body iron status, as well as in response to infections. The possibility that an enterocyte with an elevated iron concentration is more susceptible to invasion by enteric pathogens is not known. Therefore, we examined the impact of enterocyte iron status on the invasion and survival of an enteric pathogen, as well as on the levels of several cytokine and chemokine mRNAs by the host cell. The enterocyte-like Caco-2 human intestinal cell line and Salmonella enteritidis served as the models to examine the effect of iron on the host-parasite interaction. Iron status of Caco-2 cells was altered by incubation in serum-free medium supplemented with varying levels of iron. Elevated iron status of Caco-2 cells increased the efficiency of the invasion and the number of bacteria surviving in the intracellular environment. Caco-2 cells constitutively expressed transforming growth factor-beta1, interleukin-8, monocyte chemotactic protein-1, tumor necrosis factor-alpha and interleukin-1 beta, and infection with S. enteritidis increased the relative quantities of all cytokine/chemokine mRNAs except interleukin-1 beta. Elevated iron status of Caco-2 cells decreased the levels of cytokine/chemokine mRNAs by 25-45% in uninfected cells. In contrast, bacterial infection was associated with a 21-95% increase in cytokine/chemokine mRNAs levels in Caco-2 cells with higher iron concentration compared with infected cells with lower iron concentration. These data support the hypothesis that elevated enterocyte iron status increases susceptibility to infection and exacerbates the mucosal inflammatory response initiated by microbial invasion by increasing cytokine/chemokine expression.