Olthof Evelyn D, Gülich Alexandra F, Renne Mike F, Landman Sija, Joosten Leo A B, Roelofs Hennie M J, Wanten Geert J A
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.
Toxicol In Vitro. 2015 Oct;29(7):1851-8. doi: 10.1016/j.tiv.2015.07.004. Epub 2015 Jul 7.
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.
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.
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.
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.
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。
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。
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。
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。