Effect of tumor necrosis factor α, interferon γ, and interleukin-4 on bacteria-enterocyte interactions
Effect of tumor necrosis factor α, interferon γ, and interleukin-4 on bacteria-enterocyte interactions
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DOI：
10.1006/jsre.2002.6417
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发表时间：
2002-05-15
影响因子：
2.2
通讯作者：
Wells, CL
中科院分区：
文献类型：
--
作者：
Hess, DJ;Henry-Stanley, MJ;Wells, CL
背景关于细菌从肠腔移位到肠外部位的机制知之甚少。由于与脓毒症、炎症和创伤相关的细胞因子级联反应已被证明会影响肠上皮细胞的通透性，因此设计实验以阐明所选细胞因子对培养的HT-29和Caco-2肠细胞的细菌粘附和内化的影响。用肿瘤坏死因子α（TNF-α）、干扰素γ（IFN-γ）或白细胞介素-4（IL-4）预处理成熟、汇合的肠细胞48至72 h。通过酶联免疫吸附试验测定单核细胞增生李斯特菌、鼠伤寒沙门氏菌、奇异变形杆菌和大肠杆菌的粘附性，并通过庆大霉素保护试验定量细菌内化。肠上皮细胞通透性测定跨上皮电阻和40-kDa的荧光葡聚糖通量。使用在可渗透支持物上培养的肠上皮细胞测量细菌穿过融合肠上皮细胞的迁移。TNF-α、IFN-γ和YL-4对HT-29和Caco-2肠上皮细胞的细菌粘附有不同的影响，尽管最一致的发现是与INF-γ相关的细菌粘附增加。然而，这些细胞因子对Caco-2或HT-29肠细胞的细菌内化没有明显的影响。此外，通过跨上皮电阻或右旋糖酐通量测量，这些细胞因子均对融合肠细胞的渗透性没有明显影响。TNF-α、IFN-γ或IL-4均未改变HT-29肠上皮细胞的细菌迁移;然而，IL-4可持续降低Caco-2肠上皮细胞的细菌迁移。IFN-γ可以增加选定种类的肠细菌的上皮粘附，并且IL-4可以充当屏障维持剂以减少穿过肠上皮的细菌迁移。(C)2002 Elsevier Science（美国）。
Background. Little is known about the mechanisms involved in bacterial translocation from the intestinal lumen to extraintestinal sites. Because the cytokine cascade associated with sepsis, inflammation, and trauma has been shown to affect intestinal epithelial permeability, experiments were designed to clarify the effects of selected cytokines on bacterial adherence to and internalization by cultured HT-29 and Caco-2 enterocytes.Methods. Mature, confluent enterocytes were pre-treated 48 to 72 h with tumor necrosis factor alpha (TNF-alpha), interferon gamma, (IFN-gamma), or interleukin-4 (IL-4). Adherence of Listeria monocytogenes, Salmonella typhimurium, Proteus mirabilis, and Escherichia coli was measured by enzyme-linked immunosorbent assay and bacterial internalization was quantified by the gentamicin protection assay. Enterocyte permeability was measured by transepithelial electrical resistance and by flux of 40-kDa fluorescent dextran. Bacterial transmigration across confluent enterocytes was measured using enterocytes cultivated on permeable supports.Results. TNF-alpha, IFN-gamma, and YL-4 had variable effects on bacterial adherence to HT-29 and Caco-2 enterocytes, although the most consistent finding was increased bacterial adherence associated with INF-gamma. However, none of these cytokines had a noticeable effect on bacterial internalization by either Caco-2 or HT-29 enterocytes. In addition, none of these cytokines had a noticeable effect on the permeability of confluent enterocytes as measured by transepithelial electrical resistance or dextran flux. Bacterial transmigration across confluent HT-29 enterocytes was not altered by TNF-alpha, IFN-gamma, or IL-4; however, IL-4 consistently decreased bacterial transmigration across confluent Caco-2 enterocytes.Conclusions. IFN-gamma may augment the epithelial adherence of selected species of enteric bacteria, and IL-4 may act as a barrier-sustaining agent to decrease bacterial migration across the intestinal epithelium. (C) 2002 Elsevier Science (USA).