Lactoferrin downregulates pro-inflammatory cytokines upexpressed in intestinal epithelial cells infected with invasive or noninvasive Escherichia coli strains
Lactoferrin downregulates pro-inflammatory cytokines upexpressed in intestinal epithelial cells infected with invasive or noninvasive Escherichia coli strains
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DOI：
10.1139/o06-039
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发表时间：
2006-06-01
影响因子：
2.9
通讯作者：
Valenti, Piera
中科院分区：
文献类型：
--
作者：
Berlutti, Francesca;Schippa, Serena;Valenti, Piera
肠上皮细胞能够与肠道或病原微生物差异性地相互作用，分别引发生理性或破坏性炎症。为了模拟大肠杆菌-肠侵袭性细菌-宿主细胞相互作用，我们用非侵袭性大肠杆菌HB 101和重组侵袭性大肠杆菌HB 101感染Caco-2细胞。coliHB101（pRI203）。利用DNA微阵列mRNA分析和ELISA检测，我们研究了几种细胞因子和精氨酸相关基因在感染的Caco-2细胞中的表达在牛乳铁蛋白（bLf）的存在或不存在。用非侵袭性菌株感染Caco-2细胞可诱导白细胞介素8（IL-8）表达的轻微增加，而用侵袭性E. coliHB 101（pRI 203）诱导IL-8以及其他促炎细胞因子的表达显著增加。加入天然或完整形式的bLf不影响未感染的Caco-2细胞的细胞因子基因表达，但它降低了大肠杆菌HB 101感染细胞的IL-8表达。此外，除了IL-8，bLfs显着下调促炎性细胞因子的表达上调Caco-2细胞感染的侵袭性菌株。尽管IL-8被bLfs降低，但它仍然上调，表明它可能是细胞内细菌持续存在的信号。bLf减少某些促炎细胞因子表达的能力，似乎与其铁饱和度无关，可能代表了调节上皮细胞对病原菌的反应以及限制细胞损伤和感染扩散的重要天然机制。
Intestinal epithelial cells are able to differentially interact with commensal or pathogenic microorganisms, triggering a physiological or destructive inflammation, respectively. To mimic commensal-enteroinvasive bacteria-host cell interaction, we infected Caco-2 cells with noninvasive Escherichia coli HB101 and with recombinant invasive E. coli HB101(pRI203). Using DNA microarray mRNA profiling and ELISA assays, we studied the expression of several cytokine and cytokine-related genes in infected Caco-2 cells in the absence or presence of bovine lactoferrin (bLf). Infection of Caco-2 cells with the noninvasive strain induced a slight increase in the expression of interleukin 8 (IL-8), whereas infection with invasive E. coli HB101(pRI203) induced a significant increase in the expression of IL-8 as well as other pro-inflammatory cytokines. The addition of bLf, in native- or holo-form, did not influence expression of cytokine genes by uninfected Caco-2 cells, but it decreased expression of IL-8 by cells infected with E.coli HB101. Moreover, except for IL-8, bLfs dramatically downregulated pro-inflammatory cytokines upexpressed by Caco-2 cells infected with the invasive strain. Although IL-8 was decreased by bLfs, it remained upregulated, suggesting that it could be a signal of persistence of intracellular bacteria. The bLf ability to reduce expression of some pro-inflammatory cytokines, which appears independent of its iron saturation, might represent an important natural mechanism in regulating epithelial cell responses to pathogenic bacteria and in limiting cell damage and the spread of infections.