Oral deoxynivalenol exposure of pigs modulates the pathophysiological impact of a subsequent LPS-stimulus

猪的口服脱氧雪腐镰刀菌烯醇暴露调节随后的 LPS 刺激的病理生理影响

• 批准号: 5374972
• 负责人: Professor Dr. Sven Dänicke
• 金额: --
• 依托单位: Institut für Tierernährung (ITE)
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2002
• 资助国家: 德国
• 起止时间: 2001-12-31 至 2018-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/5374972?language=en
• 关键词: Oral; deoxynivalenol; exposure; pigs; modulates

In the completed project period we were able to demonstrate the detrimental effect of deoxynivalenol (DON) and lipopolysaccharide (LPS) on the in vivo protein synthesis as well as the intestinal barrier integrity in vivo and in vitro. The interaction of DON and LPS and its impact on the acute phase reaction (APR), their related cytokine expression and the subsequently induced pathophysiological effects, in particular on intestinal and hepatic tissue and immune cells, depended primarily on their route of application. LPS-induced pathohistological lesions such as haemorrhage and lymphocyte infiltration in the liver seemed to be ameliorated in pigs received a diet containing DON 5 weeks prior to LPS challenge. However, the contribution of the liver, an immunologically active organ (LPS-clearance, mediation of APR), to metabolisation and elimination of DON (conjugation, biliary excretion) could not be investigated in depth due to the fact that only peripheral venous blood was obtainable in the previous experimental setup. In order to estimate the portal influx of DON and LPS from the gastrointestinal tract (GIT) their time-dependent concentrations in the portal vein are essential. Moreover, determining orally administered trans- and paracellular markers (e.g. PEG) in the portal blood would enable an estimation of the intestinal epithelial permeability and thus of intestinal barrier integrity in vivo. Our investigations (in vitro and in vivo) demonstrated that the intestinal lining is more vulnerable to basolateral (i.e. systemic) exposure to toxins as compared to the apical side, thus knowledge of the actual arterial influx of DON and LPS to the GIT in vivo is crucial. In vitro trials we could show a significant regulation of genes (microarray) related to energy metabolism, transcription, translation as well as cell communication when porcine intestinal epithelial cells were exposed to basolateral DON whereas apical exposure of the same concentration yielded no changes. It is essential to investigate whether these changes found on a mRNA-level are reflected in their corresponding structure and function in vitro and whether this holds also true for the intestinal epithelium in vivo.Our objectives in the present project proposal are to contribute to the elucidation of the mechanisms underlying DON-associated modulation of a subsequent LPS stimulus in an advanced animal model. Particularly we will focus on the integrated action of intestinal barrier and liver in toxin absorption and metabolisation as well as on the systemic inflammatory response, reflected in the immune cell population in local and peripheral immune system.

在完成的项目期间，我们能够证明脱氧雪腐镰刀菌烯醇（DON）和脂多糖（LPS）对体内蛋白质合成以及体内和体外肠屏障完整性的有害影响。DON和LPS的相互作用及其对急性期反应（APR）的影响、它们相关的细胞因子表达和随后诱导的病理生理学效应，特别是对肠和肝组织以及免疫细胞的影响，主要取决于它们的施用途径。LPS诱导的病理组织学病变，如出血和淋巴细胞浸润的肝脏似乎得到改善，在猪接受饮食含有DON 5周前LPS的挑战。然而，由于在之前的实验设置中仅可获得外周静脉血，因此无法深入研究肝脏（免疫活性器官（LPS清除、APR介导））对DON代谢和消除（结合、胆汁排泄）的贡献。为了估计DON和LPS从胃肠道（GIT）的门静脉内流，它们在门静脉中的时间依赖性浓度是必需的。此外，测定门静脉血中口服给药的跨细胞和细胞旁标志物（例如PEG）将能够估计肠上皮通透性，从而估计体内肠屏障完整性。我们的研究（体外和体内）表明，与顶侧相比，肠衬里更容易受到基底侧（即全身性）毒素暴露的影响，因此了解体内DON和LPS向GIT的实际动脉流入至关重要。在体外实验中，我们可以显示一个显着的调控基因（微阵列）相关的能量代谢，转录，翻译以及细胞通讯时，猪肠上皮细胞暴露于基底侧DON，而顶端暴露相同浓度的没有产生变化。这是至关重要的，以调查是否在mRNA水平上发现的这些变化反映在其相应的结构和功能在体外，这是否也适用于肠上皮在vivo.Our的目标在本项目提案是有助于阐明的机制，在先进的动物模型中的后续LPS刺激的相关的DON调制。特别是，我们将重点关注肠屏障和肝脏在毒素吸收和代谢中的综合作用以及全身炎症反应，反映在局部和外周免疫系统的免疫细胞群中。

项目成果

Postweaning development of porcine small intestinal morphology and epithelial cell proliferation

• DOI: 10.2527/jas.2015-9774
• 发表时间: 2016-09
• 期刊: Journal of Animal Science
• 影响因子: 3.3
• 作者: J. Kluess;S. Kahlert;J. Krüger;H. Rothkötter;A. Berk;S. Kersten;S. Dänicke

Plasma kinetics and matrix residues of deoxynivalenol (DON) and zearalenone (ZEN) are altered in endotoxaemic pigs independent of LPS entry site

• DOI: 10.1007/s12550-017-0276-z
• 发表时间: 2017-08-01
• 期刊: MYCOTOXIN RESEARCH
• 影响因子: 3
• 作者: Bannert, Erik;Tesch, Tanja;Daenicke, Sven
• 通讯作者: Daenicke, Sven

Analytical method for the determination of polyethylenglycole 400 as marker in porcine plasma.

• DOI: 10.1016/j.jchromb.2019.03.003
• 发表时间: 2019-03
• 期刊: Journal of chromatography. B, Analytical technologies in the biomedical and life sciences
• 作者: J. Saltzmann;J. Blum;J. Kluess;S. Dänicke

On the distribution and metabolism of Fusarium-toxins along the gastrointestinal tract of endotoxaemic pigs

• DOI: 10.1080/1745039x.2018.1465261
• 发表时间: 2018-01-01
• 期刊: ARCHIVES OF ANIMAL NUTRITION
• 影响因子: 2
• 作者: Bannert, Erik;Tesch, Tanja;Daenicke, Sven
• 通讯作者: Daenicke, Sven

Relationships between body temperatures and inflammation indicators under physiological and pathophysiological conditions in pigs exposed to systemic lipopolysaccharide and dietary deoxynivalenol

• DOI: 10.1111/jpn.12684
• 发表时间: 2018-02-01
• 期刊: JOURNAL OF ANIMAL PHYSIOLOGY AND ANIMAL NUTRITION
• 影响因子: 2.7
• 作者: Tesch, T.;Bannert, E.;Daenicke, S.
• 通讯作者: Daenicke, S.