Modulation of microRNA by toll-like receptors

THESIS 9411Toll-like receptors (TLRs) play a key role regulating gene expression following the detection of a pathogen by cells to bring about an inflammatory response. I investigated whether or not activation of TLRs in dendritic cells could alter the expression patterns of microRNAs (miRNA). Analysing a panel of 150 miRNA probes, I found that stimulation of TLR2, TLR3 and TLR4 indeed up-regulated the expression of several miRNA. Up-regulation of miR-146, miR-155 and miR-21 was induced by all three TLRs. I focused my studies on the induction of miR-21 by TLRs. miR-21 was induced in dendritic cells, macrophages and importantly, human periphereal blood mononuclear cells (PBMCs). No induction of miR-21 was detected in cells deficient in MyD88 or the NFkB subunit p65