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代乳粉中的膳食花生四烯酸盐在脂多糖刺激的仔猪肺泡巨噬细胞中引发前列腺素E信号传导的双重益处。

Dietary arachidonate in milk replacer triggers dual benefits of PGE signaling in LPS-challenged piglet alveolar macrophages.

作者信息

Walter Kathleen R, Lin Xi, Jacobi Sheila K, Käser Tobias, Esposito Debora, Odle Jack

机构信息

1Department of Animal Science, Plants for Human Health Institute, North Carolina State University, Kannapolis, North Carolina USA.

2Department of Animal Science, North Carolina State University, Raleigh, North Carolina USA.

出版信息

J Anim Sci Biotechnol. 2019 Feb 15;10:13. doi: 10.1186/s40104-019-0321-1. eCollection 2019.

DOI:10.1186/s40104-019-0321-1
PMID:30815256
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6376662/
Abstract

BACKGROUND

Respiratory infections challenge the swine industry, despite common medicinal practices. The dual signaling nature of PGE (supporting both inflammation and resolution) makes it a potent regulator of immune cell function. Therefore, the use of dietary long chain n-6 PUFA to enhance PGE effects merits investigation.

METHODS

Day-old pigs ( = 60) were allotted to one of three dietary groups for 21 d ( = 20/diet), and received either a control diet (CON, arachidonate = 0.5% of total fatty acids), an arachidonate (ARA)-enriched diet (LC n-6, ARA = 2.2%), or an eicosapentaenoic (EPA)-enriched diet (LC n-3, EPA = 3.0%). Alveolar macrophages and lung parenchymal tissue were collected for fatty acid analysis. Isolated alveolar macrophages were stimulated with LPS in situ for 24 h, and mRNA was isolated to assess markers associated with inflammation and eicosanoid production. Culture media were collected to assess PGE secretion. Oxidative burst in macrophages was measured by: 1) oxygen consumption and extracellular acidification (via Seahorse), 2) cytoplasmic oxidation and 3) nitric oxide production following 4, 18, and 24 h of LPS stimulation.

RESULTS

Concentration of ARA (% of fatty acids, /) in macrophages from pigs fed LC n-6 was 86% higher than CON and 18% lower in pigs fed LC n-3 ( < 0.01). Following LPS stimulation, abundance of and mRNA ( <  0.0001), and PGE secretion ( < 0. 01) were higher in LC n-6 PAM vs. CON. However, abundance was 1.6-fold lower than CON. Macrophages from CON and LC n-6 groups were 4-fold higher in abundance ( < 0.0001) compared to LC n-3. Oxygen consumption and extracellular acidification rates increased over 4 h following LPS stimulation ( < 0.05) regardless of treatment. Similarly, increases in cytoplasmic oxidation ( < 0.001) and nitric oxide production ( <  0.002) were observed after 18 h of LPS stimulation but were unaffected by diet.

CONCLUSIONS

We infer that enriching diets with arachidonic acid may be an effective means to enhance a stronger innate immunologic response to respiratory challenges in neonatal pigs. However, further work is needed to examine long-term safety, clinical efficacy and economic viability.

摘要

背景

尽管有常见的药物治疗方法,但呼吸道感染仍对养猪业构成挑战。前列腺素E(PGE)具有双重信号特性(既支持炎症又支持炎症消退),使其成为免疫细胞功能的有效调节剂。因此,使用膳食长链n-6多不饱和脂肪酸(PUFA)来增强PGE的作用值得研究。

方法

将60只新生仔猪分配到三个日粮组中的一组,为期21天(每组20只),分别给予对照日粮(CON,花生四烯酸占总脂肪酸的0.5%)、富含花生四烯酸(ARA)的日粮(LC n-6,ARA = 2.2%)或富含二十碳五烯酸(EPA)的日粮(LC n-3,EPA = 3.0%)。收集肺泡巨噬细胞和肺实质组织进行脂肪酸分析。将分离的肺泡巨噬细胞用脂多糖(LPS)原位刺激24小时,分离mRNA以评估与炎症和类花生酸生成相关的标志物。收集培养基以评估PGE分泌。通过以下方法测量巨噬细胞中的氧化爆发:1)氧气消耗和细胞外酸化(通过海马分析仪),2)细胞质氧化,以及3)LPS刺激4、18和24小时后的一氧化氮生成。

结果

饲喂LC n-6日粮的猪巨噬细胞中ARA的浓度(占脂肪酸的百分比,/)比CON组高86%,而饲喂LC n-3日粮的猪巨噬细胞中ARA的浓度比CON组低18%(P < 0.01)。LPS刺激后,LC n-6组肺泡巨噬细胞(PAM)中IL-1β和IL-6 mRNA的丰度(P < 0.0001)以及PGE分泌(P < 0.01)均高于CON组。然而,IL-10的丰度比CON组低1.6倍。与LC n-3组相比,CON组和LC n-6组巨噬细胞中TNF-α的丰度高4倍(P < 0.0001)。无论处理如何,LPS刺激后4小时内氧气消耗和细胞外酸化率均增加(P < 0.05)。同样,LPS刺激18小时后观察到细胞质氧化增加(P < 0.001)和一氧化氮生成增加(P < 0.002),但不受日粮的影响。

结论

我们推断,在日粮中添加花生四烯酸可能是增强新生仔猪对呼吸道挑战的更强固有免疫反应的有效手段。然而,需要进一步研究以检验其长期安全性、临床疗效和经济可行性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e371/6376662/36402ed83839/40104_2019_321_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e371/6376662/841610b531bd/40104_2019_321_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e371/6376662/f413d3b6ec65/40104_2019_321_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e371/6376662/36402ed83839/40104_2019_321_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e371/6376662/841610b531bd/40104_2019_321_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e371/6376662/f413d3b6ec65/40104_2019_321_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e371/6376662/36402ed83839/40104_2019_321_Fig4_HTML.jpg

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