Zinc oxide protects cultured enterocytes from the damage induced by Escherichia coli
Zinc oxide protects cultured enterocytes from the damage induced by Escherichia coli
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DOI：
10.1093/jn/133.12.4077
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发表时间：
2003-12-01
影响因子：
4.2
通讯作者：
Mengheri, E
中科院分区：
文献类型：
--
作者：
Roselli, M;Finamore, A;Mengheri, E
有证据表明，氧化锌（ZnO）可以预防肠道疾病。然而，尽管ZnO可能具有抗菌作用，但这种保护作用的机制尚未阐明。我们研究了ZnO在保护肠细胞免受肠致病性大肠杆菌（ETEC，菌株K88）引起的损伤和相关机制的潜在益处，使用人Caco-2肠细胞。与未处理的细胞相比，0.01和1 mmol/L ZnO处理不影响细胞渗透性，测量为跨上皮电阻（TEER），并适度增加5 mmol/L ZnO。转移的C-14-菊糖略有增加5 mmol/L ZnO相比，未经处理的细胞，转移不受较低的浓度。TEER和C-14-菊糖转移在ETEC感染的细胞中低于未感染的细胞。用0.2 mmol/L ZnO处理ETEC暴露防止了膜完整性的破坏。ETEC能够粘附肠上皮细胞，并在一定程度上侵入细胞。ZnO处理减少细菌粘附并阻断细菌侵入。与未感染细胞相比，ETEC感染上调了炎性细胞因子白细胞介素-8、生长相关癌基因-α和肿瘤坏死因子-α的表达，并降低了抗炎性细胞因子转化生长因子-β的表达。加入0.2或1 mmol/LZnO可抵消ETEC引起的细胞因子mRNA水平的改变。ZnO的保护作用不是由于任何抗菌活性，因为在含有ZnO的培养基中生长的ETEC的活力不受影响。总之，ZnO可能通过抑制细菌的粘附和内化，防止紧密连接通透性的增加和调节细胞因子基因的表达来保护肠细胞免受ETEC感染。J.Nutr. 133：4077- 4082，2003.
There is some evidence that zinc oxide (ZnO) protects against intestinal diseases. However, despite the suggestions that ZnO may have an antibacterial effect, the mechanisms of this protective effect have not yet been elucidated. We investigated the potential benefits of ZnO in protecting intestinal cells from damage induced by enterotoxigenic Escherichia coli (ETEC, strain K88) and the related mechanisms, using human Caco-2 enterocytes. Cell permeability, measured as transepithelial electrical resistance (TEER), was unaffected by 0.01 and 1 mmol/L ZnO treatments and moderately increased by 5 mmol/L ZnO, compared with untreated cells. Transfer of C-14-inulin was slightly increased by 5 mmol/L ZnO compared with untreated cells; transfer was unaffected by lower concentrations. The TEER and C-14-inulin transfer were lower in ETEC-infected cells than in uninfected cells. Treatment of ETEC exposure with 0.2 mmol/L ZnO prevented disruption of membrane integrity. The ETEC was able to adhere to enterocytes and, to some extent, invade the cells. The ZnO treatment reduced bacterial adhesion and blocked bacterial invasion. The ETEC infection upregulated the expression of the inflammatory cytokines interleukin-8, growth-related oncogene-alpha and tumor necrosis factor-alpha, and reduced that of the anti-inflammatory cytokine transforming growth factor-beta, compared with uninfected cells. The addition of 0.2 or 1 mmol/L ZnO counteracted the alteration of cytokine mRNA levels caused by ETEC. The protective effects of ZnO were not due to any antibacterial activity, because the viability of ETEC grown in a medium containing ZnO was unaffected. In conclusion, ZnO may protect intestinal cells from ETEC infection by inhibiting the adhesion and internalization of bacteria, preventing the increase of tight junction permeability and modulating cytokine gene expression. J.Nutr. 133:4077-4082,2003.