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Does chronic dietary exposure to the mycotoxin deoxynivalenol affect the porcine hepatic transcriptome when an acute-phase response is initiated through first or second-pass LPS challenge of the liver?
Innate Immunity ( IF 3.2 ) Pub Date : 2021-07-31 , DOI: 10.1177/17534259211030563
Sven Dänicke 1 , Ann-Katrin Heymann 1 , Michael Oster 2 , Klaus Wimmers 2 , Tanja Tesch 1 , Erik Bannert 1 , Susanne Bühler 1 , Susanne Kersten 1 , Jana Frahm 1 , Jeannette Kluess 1 , Stefan Kahlert 3 , Hermann-Josef Rothkötter 3 , Fabian Billenkamp 1
Affiliation  

The sensitivity of pigs to deoxynivalenol (DON) might be increased by systemic inflammation (SI), which also has consequences for hepatic integrity. Liver lesions and a dys-regulated gene network might hamper hepatic handling and elimination of DON whereby the way of initiation of hepatic inflammation might play an additional role. First and second-pass exposure of the liver with LPS for triggering a SI was achieved by LPS infusion via pre- or post-hepatic venous route, respectively. Each infusion group was pre-conditioned either with a control diet (0.12 mg DON/kg diet) or with a DON-contaminated diet (4.59 mg DON/kg diet) for 4 wk. Liver transcriptome was evaluated at 195 min after starting infusions. DON exposure alone failed to modulate the mRNA expression significantly. However, pre- and post-hepatic LPS challenges prompted transcriptional responses in immune and metabolic levels. The mRNAs for B-cell lymphoma 2-like protein 11 as a key factor in apoptosis and IFN-γ released by T cells were clearly up-regulated in DON-fed group infused with LPS post-hepatically. On the other hand, mRNAs for nucleotide binding oligomerization domain containing 2, IFN-α and eukaryotic translation initiation factor 2α kinase 3 as ribosomal stress sensors were exclusively up-regulated in control pigs with pre-hepatic LPS infusion. These diverse effects were traced back to differences in TLR4 signalling.



中文翻译:

当通过肝脏的第一次或第二次 LPS 攻击引发急性期反应时,长期饮食暴露于霉菌毒素脱氧雪腐镰刀菌烯醇是否会影响猪肝脏转录组?

全身炎症 (SI) 可能会增加猪对脱氧雪腐镰刀菌烯醇 (DON) 的敏感性,这也会对肝脏完整性产生影响。肝脏病变和失调的基因网络可能会阻碍肝脏处理和消除 DON,从而引发肝脏炎症的方式可能发挥额外的作用。通过 LPS 输注通过LPS 对肝脏进行第一次和第二次暴露以触发 SI肝前或肝后静脉途径,分别。每个输注组用对照饮食(0.12 mg DON/kg 饮食)或用 DON 污染饮食(4.59 mg DON/kg 饮食)预处理 4 周。在开始输注后 195 分钟评估肝转录组。单独的 DON 暴露未能显着调节 mRNA 表达。然而,肝前和肝后 LPS 挑战促使免疫和代谢水平的转录反应。B 细胞淋巴瘤 2 样蛋白 11 的 mRNA 作为细胞凋亡的关键因素和 T 细胞释放的 IFN-γ 在肝后输注 LPS 的 DON 喂养组中明显上调。另一方面,核苷酸结合寡聚结构域的 mRNAs 含有 2,作为核糖体应激传感器的 IFN-α 和真核翻译起始因子 2α 激酶 3 在肝前 LPS 输注的对照猪中完全上调。这些不同的影响可以追溯到 TLR4 信号传导的差异。

更新日期:2021-08-01
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