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含中链甘油三酯的脂质乳剂引起的免疫激活不受n-3脂质或Toll样受体4的调节。

Immune activation by medium-chain triglyceride-containing lipid emulsions is not modulated by n-3 lipids or toll-like receptor 4.

作者信息

Olthof Evelyn D, Gülich Alexandra F, Renne Mike F, Landman Sija, Joosten Leo A B, Roelofs Hennie M J, Wanten Geert J A

机构信息

Intestinal Failure Unit, Department of Gastroenterology and Hepatology, Radboud University Medical Center, Nijmegen, The Netherlands.

Intestinal Failure Unit, Department of Gastroenterology and Hepatology, Radboud University Medical Center, Nijmegen, The Netherlands; Membrane Biochemistry & Biophysics, Bijvoet Center for Biomolecular Research and Institute of Biomembranes, Utrecht University, Utrecht, The Netherlands.

出版信息

Toxicol In Vitro. 2015 Oct;29(7):1851-8. doi: 10.1016/j.tiv.2015.07.004. Epub 2015 Jul 7.

Abstract

BACKGROUND

Saturated medium-chain triglycerides (MCT) as part of the parenteral lipid regimen (50% MCT and 50% long chain triglycerides (LCT)) activate the immune system in vitro. Fish oil (FO)-derived n-3 fatty acids (FA) inhibit saturated FA-induced immune activation via a toll-like receptor (TLR)-4 mediated mechanism. We hypothesized that effects of parenteral MCTs on immune cells involve TLR-4 signaling and that these effects are modulated by n-3 FA that are present in FO.

MATERIALS AND METHODS

To test this hypothesis we assessed effects of addition of various commercially available mixed parenteral lipid emulsions, n-3 FA and of TLR-4 inhibition on MCT-induced human immune cell activation by evaluation of the expression of leukocyte membrane activation markers and reactive oxygen species (ROS) production.

RESULTS

All MCT-containing lipid emulsions activated leukocytes by inducing changes in expression of membrane markers and stimulus induced ROS production, whereas MCT-free lipid emulsions lacked this effect. Moreover, addition of n-3 FA to LCT/MCT did not prevent MCT-induced immune activation. TLR-4 inhibitors did not distinctly modulate MCT-induced changes in immune function.

CONCLUSION

Taken together, these findings suggest that leukocyte activation by parenteral MCTs does not involve TLR-4 signaling and is not modulated by n-3 FA in FO-, but is exerted via different signaling pathways.

摘要

背景

饱和中链甘油三酯(MCT)作为肠外脂质方案的一部分(50% MCT和50%长链甘油三酯(LCT))在体外可激活免疫系统。鱼油(FO)衍生的n-3脂肪酸(FA)通过Toll样受体(TLR)-4介导的机制抑制饱和脂肪酸诱导的免疫激活。我们假设肠外MCT对免疫细胞的作用涉及TLR-4信号传导,并且这些作用受到FO中存在的n-3 FA的调节。

材料与方法

为了验证这一假设,我们通过评估白细胞膜激活标志物的表达和活性氧(ROS)的产生,来评估添加各种市售混合肠外脂质乳剂、n-3 FA以及抑制TLR-4对MCT诱导的人类免疫细胞激活的影响。

结果

所有含MCT的脂质乳剂均通过诱导膜标志物表达的变化和刺激诱导ROS产生来激活白细胞,而不含MCT的脂质乳剂则没有这种作用。此外,向LCT/MCT中添加n-3 FA并不能阻止MCT诱导的免疫激活。TLR-4抑制剂并没有明显调节MCT诱导的免疫功能变化。

结论

综上所述,这些发现表明肠外MCT激活白细胞不涉及TLR-4信号传导,也不受FO中n-3 FA的调节,而是通过不同的信号通路发挥作用。

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