O'Driscoll David N, De Santi Chiara, McKiernan Paul J, McEneaney Victoria, Molloy Eleanor J, Greene Catherine M
Neonatology, National Maternity Hospital, Dublin, Ireland.
Respiratory Research, Department of Medicine, Royal College of Surgeons in Ireland, Education and Research Centre, Beaumont Hospital, Dublin, Ireland.
Pediatr Res. 2017 May;81(5):831-837. doi: 10.1038/pr.2017.2. Epub 2017 Jan 6.
Male neonates display poorer disease prognosis and outcomes compared with females. Immune genes which exhibit higher expression in umbilical cord blood (UCB) of females may contribute to the female immune advantage during infection and inflammation. The aim of this study was to quantify expression of Toll-like receptor (TLR) 4 signaling genes encoded on the X-chromosome in UCB from term female vs. male neonates.
UCB samples were collected from term neonates (n = 26) born by elective Caesarean section and whole blood was collected from adults (n = 20). Leukocyte RNA was isolated and used in quantitative PCR reactions for IκB kinase γ (IKKγ), Bruton's tyrosine kinase (BTK), and IL-1 receptor associated kinase (IRAK)1. IRAK1 protein was analyzed by Western blot and confocal microscopy.
In neonates there was no significant difference in the relative expression of IKKγ or BTK mRNA between genders. IRAK1 gene and protein expression was significantly higher in female vs. male UCB, with increased cytosolic IRAK1 expression also evident in female UCB mononuclear cells. Adults had higher expression of all three genes compared with neonates.
Increased expression of IRAK1 could be responsible, in part, for sex-specific responses to infection and subsequent immune advantage in female neonates.
与女性相比，男性新生儿的疾病预后和结局较差。在女性脐带血（UCB）中表达较高的免疫基因可能有助于女性在感染和炎症期间的免疫优势。本研究的目的是量化足月女性与男性新生儿UCB中X染色体上编码的Toll样受体（TLR）4信号基因的表达。
从择期剖宫产出生的足月新生儿（n = 26）中采集UCB样本，并从成年人（n = 20）中采集全血。分离白细胞RNA，并用于IκB激酶γ（IKKγ）、布鲁顿酪氨酸激酶（BTK）和IL-1受体相关激酶（IRAK）1的定量PCR反应。通过蛋白质印迹和共聚焦显微镜分析IRAK1蛋白。
在新生儿中，性别之间IKKγ或BTK mRNA的相对表达没有显著差异。女性UCB中IRAK1基因和蛋白表达明显高于男性，女性UCB单核细胞中胞质IRAK1表达增加也很明显。与新生儿相比，成年人这三个基因的表达更高。
IRAK1表达增加可能部分导致女性新生儿对感染的性别特异性反应及随后的免疫优势。
