Butyrate upregulates endogenous host defense peptides to enhance disease resistance in piglets via histone deacetylase inhibition.
Butyrate upregulates endogenous host defense peptides to enhance disease resistance in piglets via histone deacetylase inhibition.
复制标题
丁酸盐上调内源性宿主防御肽，通过组蛋白脱乙酰酶抑制增强仔猪的抗病能力
DOI：
10.1038/srep27070
复制
发表时间：
2016-05-27
影响因子：
4.6
通讯作者：
Du H
中科院分区：
文献类型：
--
作者：
Xiong H;Guo B;Gan Z;Song D;Lu Z;Yi H;Wu Y;Wang Y;Du H
丁酸盐已被用于治疗不同的炎症性疾病，具有积极的结果，丁酸盐发挥其抗炎作用的机制在很大程度上仍不清楚。本文提出了丁酸调控内源性宿主防御肽（HDPs）清除大肠杆菌O 157：H7，从而影响炎症缓解的新机制。本试验在断奶前2天用丁酸盐（占日粮的0.2%）处理仔猪。colio 157：H7攻毒试验研究猪HDP的表达、炎症反应和E.粪便中大肠杆菌157：H7载量。探讨丁酸诱导HDP基因表达的机制，以及丁酸对巨噬细胞3D 4/2体外抗菌活性和细菌清除的影响。丁酸治疗（i）可减轻E.大肠杆菌157：H7诱导的溶血性尿毒综合征（HUS）和肠道炎症的严重程度;粪便中大肠杆菌157：H7载量;（iii）通过组蛋白脱乙酰酶（HDAC）抑制，在体外和体内显著上调多种但不是全部的HDPs;和（iv）增强3D 4/2细胞的抗菌活性和细菌清除。结果表明，丁酸盐能增强抗病性，促进E. colio 157：H7，并通过HDAC抑制作用影响HDP表达，部分缓解HUS和炎症的临床症状。
Butyrate has been used to treat different inflammatory disease with positive outcomes, the mechanisms by which butyrate exerts its anti-inflammatory effects remain largely undefined. Here we proposed a new mechanism that butyrate manipulate endogenous host defense peptides (HDPs) which contributes to the elimination ofEscherichia coliO157:H7, and thus affects the alleviation of inflammation. An experiment in piglets treated with butyrate (0.2% of diets) 2 days beforeE. coliO157:H7 challenge was designed to investigate porcine HDP expression, inflammation andE. coliO157:H7 load in feces. The mechanisms underlying butyrate-induced HDP gene expression and the antibacterial activity and bacterial clearance of macrophage 3D4/2 cellsin vitrowere examined. Butyrate treatment (i) alleviated the clinical symptoms ofE. coliO157:H7-induced hemolytic uremic syndrome (HUS) and the severity of intestinal inflammation; (ii) reduced theE. coliO157:H7 load in feces; (iii) significantly upregulated multiple, but not all, HDPsin vitroandin vivovia histone deacetylase (HDAC) inhibition; and (iv) enhanced the antibacterial activity and bacterial clearance of 3D4/2 cells. Our findings indicate that butyrate enhances disease resistance, promotes the clearance ofE. coliO157:H7, and alleviates the clinical symptoms of HUS and inflammation, partially, by affecting HDP expression via HDAC inhibition.