miRNA-125b regulates TNF-α production in CD14+ neonatal monocytes via post-transcriptional regulation

Journal of Leukocyte Biology

Chia-Yo Ou²  Te-Yao Hsu and²  Kuender D. Yang ¹  Li-Tung Huang³  Ron-Fu Chen¹  I-Chun Lin³  Hui-Chen Huang³  Hsin-Chun Huang³  Hong-Ren Yu³ 

[1]  Department of Pediatrics, Chang Bing Show Chwan Memorial Hospital, Changhua, Taiwan Obstetrics, Kaohsiung Chang Gung Memorial Hospital and Graduate Institute of Clinical Medical Science, Chang Gung University College of Medicine, Kaohsiung, Taiwan;Obstetrics, Kaohsiung Chang Gung Memorial Hospital and Graduate Institute of Clinical Medical Science, Chang Gung University College of Medicine, Kaohsiung, Taiwan;Departments of Pediatrics and Obstetrics, Kaohsiung Chang Gung Memorial Hospital and Graduate Institute of Clinical Medical Science, Chang Gung University College of Medicine, Kaohsiung, Taiwan;

关键词: epigenetics;    neonate;    sepsis;    cord blood;   

DOI  :  10.1189/jlb.1211593

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

Neonates, although deficient in cell immunity, frequently reveal sepsis with augmented proinflammatory reactions. Here, we found that neonatal monocytes produced significantly higher TNF-α mRNA and protein than adult monocytes. Assessment of the transcriptional factor found no significant difference of NF-κB p65 level between neonatal and adult monocytes. Addition of Act D to access the half-life of TNF-α mRNA revealed no significant difference of the LPS-induced TNF-α mRNA half-life between them, whereas CHX increased neonatal TNF-α mRNA significantly. This suggests that a post-transcriptional mechanism involves the augmentation of TNF-α production by neonatal monocytes. To examine whether miRNA was involved in the post-transcriptional regulation, differential displays of miRNA array between neonatal and adult MNCs were performed, along with the discovery of hsa-miR-103, hsa-miR-125b, hsa-miR-130a, hsa-miR-454-3p, and hsa-miR-542-3p, which were greater than a twofold decrease or increase after LPS treatment for 4 h. The functional validation identified that miR-125b decreased significantly in association with higher TNF-α expression by neonatal monocytes after LPS stimulation. Transfection of the miR-125b precursor into neonatal monocytes significantly repressed the TNF-α mRNA and protein expression, suggesting that miR-125b negatively regulates TNF-α expression in neonatal monocytes. Modulation of miRNA expression may be used to regulate TNF-α production in newborns with altered proinflammatory reactions.

【 授权许可】

Unknown