Title page for etd-0129113-122530


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URN etd-0129113-122530
Author Hui-Chen Huang
Author's Email Address No Public.
Statistics This thesis had been viewed 5570 times. Download 448 times.
Department Biological Sciences
Year 2012
Semester 1
Degree Master
Type of Document
Language zh-TW.Big5 Chinese
Title miRNA-142-3p regulates interleukin-6 production in neonatal cord blood PMNs via posttranscriptional regulation
Date of Defense 2013-01-07
Page Count 62
Keyword
  • IL-6
  • LPS
  • miRNA-142-3p
  • PMNs
  • Human umbilical cord blood
  • Abstract Neonates are particularly susceptible to sepsis than older children and adults, and are prone to morbidity and mortality in sepsis. Broad deficits across both innate and adaptive immune functions in neonates had been identified. However, it was found that IL-6, IL-8, TNF-α levels increased significantly in septic neonates. This suggests that altered but not deficient proinflammatory response is involved in neonatal infections. The microRNAs (miRNAs), contributing to the regulation of inflammation by repressing gene expression at the posttranscriptional level, have been linked to various immune responses, however, information on the regulation of miRNA in neonatal neutrophils (PMNs) in response to endotoxin is lacking. We investigated the differented IL-6 response of PMNs to endotoxin between newborns and adults, and studied the mechanism of augmented IL-6 production by neonatal PMNs. Our results found that cord blood PMNs expressed significantly higher IL-6 mRNA and protein than adult PMNs after stimulation by endotoxin. Addition of Actinomycin D (ActD) to assess the half-life of IL-6 mRNA revealed no significant difference of the LPS-induced IL-6 mRNA half-life between adult and neonatal, whereas addition of cycloheximide ( CHX ) found increase neonatal IL-6 mRNA significantly. This suggested that posttranscriptional mechanism involved the augmentation of IL-6 expression by neonatal PMNs. The functional validation identified that decrease of miR-142-3p was significantly associated with the higher IL-6 expression by umbilical cord blood PMNs after LPS stimulation. Transfection of the miR-142-3p precursor into umbilical cord blood PMNs significantly repressed the IL-6 mRNA and protein expression, suggesting that lower miR-142-3p expression associated with negative regulation of IL-6 production is involved in LPS stimulation of neonatal PMNs activation. Modulation of miRNA expression may be used to regulate IL-6 production in newborns with altered proinflammatory reactions.
    Advisory Committee
  • Hsin-Chun Huang - chair
  • Chung-Jen Chen - co-chair
  • Kuender.D Yang - advisor
  • Jiin-Tsuey Cheng - advisor
  • Files
  • etd-0129113-122530.pdf
  • Indicate in-campus at 5 year and off-campus access at 5 year.
    Date of Submission 2013-01-29

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