Genomics

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MicroRNA profiling in human macrophages under immunogenic treatments in vitro


ABSTRACT: MicroRNAs (miRs) contribute to both neuronal and immune cell fate, but their involvement in inter-tissue communication remained unexplored. The brain, via vagal secretion of acetylcholine (ACh), suppresses peripheral inflammation by intercepting cytokine production; therefore, we predicted that microRNAs targeting acetylcholinesterase (AChE) can attenuate inflammation. Here, we report that inflammatory stimuli induce leukocyte over-expression of the AChE-targeting miR-132. Injected LNA-modified anti-miR-132 oligonucleotide depleted miR-132 levels while elevating AChE in mouse circulation and tissues. In transfected cells, a mutated 3’UTR miR-132 binding site increased AChE mRNA expression, whereas cells infected with a lentivirus expressing pre-miR-132 showed suppressed AChE. Transgenic mice over-expressing 3'UTR-null AChE showed excessive inflammatory mediators and impaired cholinergic anti-inflammatory regulation, in spite of substantial miR-132 up-regulation in brain and bone marrow. Our findings identify the AChE mRNA-targeting miR-132 as a functional regulator of the brain-to-body resolution of inflammation, opening new avenues for study and therapeutic manipulations of the neuro-immune dialogue.

ORGANISM(S): Mus musculus Homo sapiens

PROVIDER: GSE19094 | GEO | 2009/11/24

SECONDARY ACCESSION(S): PRJNA120517

REPOSITORIES: GEO

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