Enteral and parenteral nutrition distinctively modulate intestinal permeability and T cell function in vitro

Enteral and parenteral nutrition distinctively modulate intestinal permeability and T cell function in vitro
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DOI:
10.1007/s00394-008-0754-3
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发表时间:
2009-02-01
影响因子:
5
通讯作者:
Sturm, Andreas
Sturm, Andreas
中科院分区:
医学2区
文献类型:
--
作者:
Guzy, Claudia;Schirbel, Anja;Sturm, Andreas

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营养支持是治疗各种适应症的既定要素。然而,其对粘膜屏障功能的影响尚不清楚。我们研究了EN和PN对肠上皮细胞和外周血(PBMC)以及固有层单核细胞(LPMC)的影响,这些细胞都参与粘膜防御细菌易位和全身炎症。在1% EN、PN和肠外氨基酸混合物(AM)存在的情况下,用Caco-2融合单层的经上皮电阻(TER)测量上皮细胞的完整性。为了确定伤口愈合能力,使用了一个已建立的带有IEC-6细胞的迁移模型。此外,我们还研究了Caco-2、HT29以及受刺激的PBMC和LPMC的凋亡、细胞活化、增殖和细胞因子分泌。我们证明了EN、AM和PN促进上皮单层的完整性,并依赖和不依赖tgf - β重建上皮细胞的连续性。有趣的是,只有PN诱导细胞凋亡并降低线粒体膜电位。EN和AM可显著降低PBMC的激活状态。具体来说,EN导致细胞凋亡率升高,抑制细胞周期进程,增加促炎细胞因子分泌。EN和PN均可降低促炎性和抗炎性细胞因子的激活状态和释放。我们的研究提供了证据,通过促进伤口愈合和调节T细胞功能,EN, AM和PN有效地与肠道屏障和免疫系统相互作用,从而证明其用于伴随粘膜屏障功能受损的疾病。
Nutritional support is an established element of therapy for various indications. However, its impact on the mucosal barrier function is not well understood.We investigated the influence of EN and PN on intestinal epithelial cells and peripheral blood (PBMC) and lamina propria mononuclear cells (LPMC), all of which are involved in the mucosal defense against bacterial translocation and systemic inflammation.Integrity of epithelial cells was measured as transepithelial electrical resistance (TER) of confluent Caco-2 monolayers in the presence of 1% EN, PN and a parenteral amino acid mixture (AM). To determine wound healing capacities, an established migration model with IEC-6 cells was used. Furthermore, we investigated apoptosis, cell activation, proliferation and cytokine secretion of Caco-2, HT29 and of stimulated PBMC and LPMC cultured with or without 1 and 5% EN, AM or PN.We demonstrated that EN, AM and PN promoted the integrity of the epithelial monolayer and reconstituted epithelial cell continuity TGF-beta-dependently and -independently. Interestingly, only PN induced apoptosis and decreased the mitochondrial membrane potential. The activation status of PBMC was significantly reduced by EN and AM. Specifically, EN leads to an increased apoptosis rate, inhibited cell cycle progression and increased pro-inflammatory cytokine secretion. Both EN and PN reduced the activation status and the release of pro- and anti-inflammatory cytokines.Our study provides evidence that by promoting wound healing and regulating T cell function, EN, AM, and PN potently interact with the intestinal barrier and immune system, thus justifying its use in diseases accompanied by impaired mucosal barrier function.