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Int J Biol Sci 2017; 13(6):690-700. doi:10.7150/ijbs.17030

Research Paper

MicroRNA-142-3p and let-7g Negatively Regulates Augmented IL-6 Production in Neonatal Polymorphonuclear Leukocytes

Hsin-Chun Huang1, 2, Hong-Ren Yu1, Te-Yao Hsu3, I-Lun Chen1, 4, Hui-Chen Huang1, Jen-Chieh Chang1, Kuender D. Yang5✉

1. Department of Pediatrics, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 833, Kaohsiung, Taiwan
2. School of Traditional Chinese Medicine, College of Medicine, Chang Gung University, Linkou, Taiwan
3. Department of Obstetrics, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 833, Kaohsiung, Taiwan
4. Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
5. Department of Pediatrics, Mackay Memorial Hospital, Tamshui, Taiwan
6. Institute of Clinical Medical Sciences, National Yang Ming University, Taipei, Taiwan

Abstract

Neonatal PMN are qualitatively impaired in functions, yet they frequently reveal augmented inflammatory reactions during sepsis. Here, we hypothesized that PMN from newborns produce more IL-6 than those from adults under LPS stimulation, in which transcriptional or posttranscriptional regulation is involved in the altered expression. We found that neonatal PMN produced significantly higher IL-6 mRNA and protein than adult PMN. The higher IL-6 expression was not related to transcriptional but posttranscriptional regulation as the IL-6 expression was affected by the addition of cycloheximide but not actinomycin. To examine whether miRNA was involved in the IL-6 regulation of neonatal PMN, we surveyed differential displays of miRNAs that could potentially regulate IL-6 expression before and after LPS stimulation. Four miRNAs: hsa-miR-26a, hsa-miR-26b, hsa-miR-142-3p and hsa-let 7g decreased or increased after LPS treatment for 4 h. Further validation by qRT-PCR identified miR-26b, miR-142-3p and let-7g significantly changed in neonatal PMN after LPS stimulation. The functional verification by transfection of miR-142-3p and let-7g precursors into neonatal PMN significantly repressed the IL-6 mRNA and protein expression, suggesting that miR-142-3p and let-7g negatively regulate IL-6 expression in neonatal PMNs. Modulation of miRNA expression may be used to regulate IL-6 production in newborns with altered inflammatory reactions.

Keywords: miR-142-3p, let-7g, polymorphonuclear leukocytes, cord blood, IL-6, sepsis.

This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) license (https://creativecommons.org/licenses/by-nc/4.0/). See http://ivyspring.com/terms for full terms and conditions.
How to cite this article:
Huang HC, Yu HR, Hsu TY, Chen IL, Huang HC, Chang JC, Yang KD. MicroRNA-142-3p and let-7g Negatively Regulates Augmented IL-6 Production in Neonatal Polymorphonuclear Leukocytes. Int J Biol Sci 2017; 13(6):690-700. doi:10.7150/ijbs.17030. Available from http://www.ijbs.com/v13p0690.htm