Functional Validation of Immunodeficient microRNA in Neonates

Human neonates are known to be susceptible to many pathogen infections and to have altered immunity. However, the mechanisms underlying their susceptibility are still incompletely defined. It was found that IL-6, IL-8, TNF-α increased significantly in septic neonates. Our study had shown that neonatal cord blood release significantly higher TNF-α after stimulated with endotoxin and was controlled by post-transcriptional up-regulation (Huang HC & Yu HR, et al. J Leukoc Biol. 2012). We also validated a decrease in adenosine deaminase (ADA) and an increase in arginase-1 (ARG1) in neonatal monocytes and polymorphonuclear cells, respectively (Yu HR, et al. Proteomics. 2011). These differences contributed to the higher adenosine and lower L-arginine levels and induced a skewed immune reaction in newborns (Yu HR, et al. ScientificWorldJournal. 2012). MicroRNAs (miRNAs) are small, noncoding RNAs of 18–25 nt that regulate gene expression in a sequence-specific manner. MiRNAs are involved in the regulation of many key biological processes. Binding of mature miRNAs to messenger RNAs (mRNAs) negatively influences the expression of specific proteins by either degradation of the bound mRNA target or direct translational inhibition. MiRNAs are predicted to constitute ~3% of human genes and they may contribute to the post-transcriptional regulation of at least one-third of the human mRNAs. In this study, we hypothesize that miRNAs play a role in the post-transcriptional regulation of ADA and ARG1 mRNA in neonatal and adult monocytes. In order to clarify the roles of miRNAs in the post-transcriptional regulation of ADA, ARG1 and other immundeficient molecules in neonatal leukocytes. This study is designed to complete the following specific aims: 1. To explore the distinct miRNAs profiles between neonatal and adult in different leukocytes sub-populations and validation with RT-PCR 2. To enhance neonatal monocytes ADA/TNF-a signaling pathway by modulation of ADA related miRNAs 3. To correct the neonatal altered Th1/Th2 signaling pathway by modulation of ARG1 related miRNAs The purpose of this study will provide a new insight in the involvement of miRNA in the post-transcriptional regulation of skewed immune reaction in newborn. This may provide therapeutic targets for precise and specific fine-tuning of Th1/Th2 response in newborns.

Project ID:PC10401-0149
External Project ID:NSC102-2314-B182-066-MY3