Induction of porcine host defense peptide gene expression by short-chain fatty acids and their analogs.

Induction of porcine host defense peptide gene expression by short-chain fatty acids and their analogs.
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DOI:
10.1371/journal.pone.0072922
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发表时间:
2013
期刊:
影响因子:
3.7
通讯作者:
Zhang G
Zhang G
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Zeng X;Sunkara LT;Jiang W;Bible M;Carter S;Ma X;Qiao S;Zhang G

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膳食调节内源性宿主防御肽(HDPs)的合成代表了一种用于疾病控制和预防的新型抗菌方法,特别是针对耐药性感染。然而,饮食化合物如丁酸盐对HDP的调节是物种依赖性的。为了检查丁酸盐是否可以诱导猪中的HDP表达,我们通过实时PCR评估了响应丁酸钠处理的IPEC-J2肠上皮细胞、3D 4/31巨噬细胞和原代单核细胞中的一组猪HDP的表达。我们发现,丁酸是一个有效的诱导剂的多个,但不是所有的,HDP基因。猪β-防御素2(pBD 2)、pBD 3、附睾蛋白2剪接变体C(pEP 2C)和protegrins在丁酸盐反应中被显著诱导,而pBD 1表达在任何细胞类型中基本保持不变。此外,不同脂肪链长度的饱和游离脂肪酸之间的HDP诱导功效的比较揭示,含有3-8个碳的脂肪酸显示出在IPEC-J2细胞中HDP表达的明显诱导,其中丁酸盐是最有效的,长链脂肪酸仅具有边际效应。我们进一步研究了一组丁酸酯类似物在HDP诱导中的功效,发现三丁酸甘油酯、丁酸苄酯和4-苯基丁酸酯与丁酸酯相当。丁酸盐和几种类似物的鉴定具有很强的诱导猪HDP基因表达的能力,为进一步评估其作为抗生素的新替代品在增强猪先天免疫和抗病性方面的潜力提供了有吸引力的候选物。
Dietary modulation of the synthesis of endogenous host defense peptides (HDPs) represents a novel antimicrobial approach for disease control and prevention, particularly against antibiotic-resistant infections. However, HDP regulation by dietary compounds such as butyrate is species-dependent. To examine whether butyrate could induce HDP expression in pigs, we evaluated the expressions of a panel of porcine HDPs in IPEC-J2 intestinal epithelial cells, 3D4/31 macrophages, and primary monocytes in response to sodium butyrate treatment by real-time PCR. We revealed that butyrate is a potent inducer of multiple, but not all, HDP genes. Porcine β-defensin 2 (pBD2), pBD3, epididymis protein 2 splicing variant C (pEP2C), and protegrins were induced markedly in response to butyrate, whereas pBD1 expression remained largely unaltered in any cell type. Additionally, a comparison of the HDP-inducing efficacy among saturated free fatty acids of different aliphatic chain lengths revealed that fatty acids containing 3–8 carbons showed an obvious induction of HDP expression in IPEC-J2 cells, with butyrate being the most potent and long-chain fatty acids having only a marginal effect. We further investigated a panel of butyrate analogs for their efficacy in HDP induction, and found glyceryl tributyrate, benzyl butyrate, and 4-phenylbutyrate to be comparable with butyrate. Identification of butyrate and several analogs with a strong capacity to induce HDP gene expression in pigs provides attractive candidates for further evaluation of their potential as novel alternatives to antibiotics in augmenting innate immunity and disease resistance of pigs.
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