MicroRNA-146: tiny player in neonatal innate immunity?
BACKGROUND
Concise regulation of the Toll signaling pathway is mandatory in neonatal innate immunity. The microRNA-146 family (miR-146a/b) was recently reported to be a regulator of Toll-like receptor 4 (TLR4) through a negative feedback loop mechanism. Acting as a potent regulator, miRNA helps to protect the organism from developing overwhelming proinflammatory immune responses leading to septic shock or chronic inflammatory diseases.


OBJECTIVE
We investigated for the first time whether miRNA-146a/b plays a regulatory role in human monocytes derived from infant cord or adult blood, and whether differences in miRNA-146 expression exist.


METHODS
Expression profiles of miR-146a/b and TLR4 were studied by real-time PCR upon stimulation with lipopolysaccharide.


RESULTS
Both members of the miRNA-146 family showed a time-dependent upregulation. For miR-146a, a statistically higher significant increase was found after 24 h of stimulation in monocytes from cord blood compared to those derived from adults. In contrast, no differences were found for miR-146b and TLR4, respectively.


CONCLUSIONS
We conclude that differences between the negative regulatory role for miR-146a obviously exist in neonatal and adult TLR4 signaling, and suggest that more intense research in the involvement of miRNA in immune regulation will facilitate the understanding of the development and function of the innate immune system of neonates.
Lederhuber
Hans
H
Laboratory for Inherited Metabolic Disorders, Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, Vienna, Austria.
Baer
Katharina
K
Altiok
Ipek
I
Sadeghi
Kambis
K
Herkner
Kurt R
KR
Kasper
David C
DC
D000328:Adult; D002478:Cells, Cultured; D005312:Fetal Blood / Q000166:cytology; D020869:Gene Expression Profiling; D006801:Humans; D007113:Immunity, Innate / Q000502:physiology*; D007231:Infant, Newborn; D016753:Interleukin-10 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D035683:MicroRNAs / Q000502:physiology*; D009000:Monocytes / Q000187:drug effects / Q000276:immunology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000276:immunology
C508609:IL10 protein, human; C508600:IL6 protein, human; D015850:Interleukin-6; D008070:Lipopolysaccharides; C542542:MIRN146 microRNA, human; D035683:MicroRNAs; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D016753:Interleukin-10