Inverse relationship between microRNA-155 and -184 expression with increasing conjunctival inflammation during ocular Chlamydia trachomatis infection.
Inverse relationship between microRNA-155 and -184 expression with increasing conjunctival inflammation during ocular Chlamydia trachomatis infection.
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DOI：
10.1186/s12879-016-1367-8
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发表时间：
2016-02-03
影响因子：
3.7
通讯作者：
Holland MJ
中科院分区：
文献类型：
--
作者：
Derrick T;Last AR;Burr SE;Roberts CH;Nabicassa M;Cassama E;Bailey RL;Mabey DC;Burton MJ;Holland MJ
沙眼是一种可预防的致盲性眼病，由沙眼衣原体（Ct）眼部感染引起。我们先前发现microRNAs（miR）-147b和miR-1285在炎症性沙眼瘢痕形成中上调。在疾病的初始阶段，目前Ct感染的滤泡性沙眼，miR的差异表达尚未研究。结膜样本收集自163名1 - 9岁儿童，他们生活在西非几内亚比绍的沙眼流行区。对来自5名患有滤泡性沙眼且当前Ct感染的儿童和5名健康结膜且无Ct感染的儿童的样本进行小RNA测序（RNAseq）。小RNAseq还在体外用眼部Ct菌株A2497和无等基因质粒A2497感染的人上皮细胞系上进行。在163个临床样本中通过定量PCR（qPCR）验证结果。RNAseq数据的差异表达鉴定了12种在滤泡性沙眼期间相对表达发生变化的miR，其中9种经qPCR确认为差异表达（miR-155、miR-150、miR-142、miR-181b、miR-181a、miR-342、miR-132、miR-4728和miR-184）。miR-155和miR-184的表达与临床炎症程度有直接关系。随着临床炎症严重程度的增加，miR-155上调（OR = 2.533（（95% CI = 1.291 - 4.971）; P = 0.0069），miR-184下调（OR = 0.416（（95% CI = 0.300 - 0.578）; P = 1.61 * 10 − 7）。在体外用Ct感染后48 h，在HEp-2或HCjE上皮细胞中未检测到差异miR表达。与HEp-2细胞相比，结膜上皮细胞系HCjE细胞具有显著不同的miR背景表达。在滤泡性沙眼中，miR-155和miR-184的表达与炎症的严重程度相关。这可能反映了宿主对免疫应答的调节以及Ct清除后伤口愈合的延长期。愈合时间延长可能与随后的瘢痕性沙眼的发展有关。本文的在线版本（doi：10.1186/s12879 - 016 - 1367 - 8）包含补充材料，可供授权用户使用。
Trachoma, a preventable blinding eye disease, is initiated by ocular infection with Chlamydia trachomatis (Ct). We previously showed that microRNAs (miR) -147b and miR-1285 were up-regulated in inflammatory trachomatous scarring. During the initial stage of disease, follicular trachoma with current Ct infection, the differential expression of miR has not yet been investigated. Conjunctival samples were collected from 163 children aged 1–9 years old living in a trachoma-endemic region of Guinea Bissau, West Africa. Small RNA sequencing (RNAseq) was carried out on samples from five children with follicular trachoma and current Ct infection and five children with healthy conjunctivae and no Ct infection. Small RNAseq was also carried out on human epithelial cell lines infected with ocular Ct strains A2497 and isogenic plasmid-free A2497 in vitro. Results were validated by quantitative PCR (qPCR) in 163 clinical samples. Differential expression of RNAseq data identified 12 miR with changes in relative expression during follicular trachoma, of which 9 were confirmed as differentially expressed by qPCR (miR-155, miR-150, miR-142, miR-181b, miR-181a, miR-342, miR-132, miR-4728 and miR-184). MiR-155 and miR-184 expression had a direct relationship with the degree of clinical inflammation. MiR-155 was up-regulated (OR = 2.533 ((95 % CI = 1.291–4.971); P = 0.0069) and miR-184 was down-regulated (OR = 0.416 ((95 % CI = 0.300–0.578); P = 1.61*10−7) as the severity of clinical inflammation increased. Differential miR expression was not detected in HEp-2 or HCjE epithelial cells 48 h post infection with Ct in vitro. HCjE cells, a conjunctival epithelial cell line, had a markedly different miR background expression compared to HEp-2 cells. In follicular trachoma, expression of miR-155 and miR-184 is correlated with the severity of inflammation. This likely reflects host regulation of the immune response and a prolonged period of wound healing following the clearance of Ct. Prolonged healing may be associated with subsequent development of scarring trachoma. The online version of this article (doi:10.1186/s12879-016-1367-8) contains supplementary material, which is available to authorized users.