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MicroRNA-132 Potentiates Cholinergic Anti-Inflammatory Signaling by Targeting Acetylcholinesterase

Shaked, Iftach, Meerson, Ari, Wolf, Yochai, Avni, Ran, Greenberg, David, Gilboa-Geffen, Adi, Soreq, Hermona·2009·Immunity
DOI 10.1016/j.immuni.2009.09.019
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Abstract

MicroRNAs (miRNAs) contribute to both neuronal and immune cell fate, but their involvement in intertissue 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 induced leukocyte overexpression of the AChE-targeting miR-132. Injected locked nucleic acid (LNA)-modified anti-miR-132 oligonucleotide depleted miR-132 amounts 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 overexpressing 3'UTR null AChE showed excessive inflammatory mediators and impaired cholinergic anti-inflammatory regulation, in spite of substantial miR-132 upregulation 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 avenues for study and therapeutic manipulations of the neuro-immune dialog.

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  • miR-132 has anti-inflammatory properties, including direct targeting of acetylcholinesterase and regulation of key inflammatory pathways like TLR4 and NF-kB.

    “Anti-inflammatory properties of miR-132 have been demonstrated in multiple independent in vitro and in vivo studies, including its direct targeting of acetylcholinesterase (which leads to increased levels of acetylcholine and, thereby, inhibits the release of pro-inflammatory cytokines), and its regulation over key inflammatory pathways, like TLR4 and NF-kB, which we also observed in our study [41”

    From microRNA-132 attenuates inflammation in induced pluripotent stem cell-derived microglia from Alzheimer’s disease patients (2026) · cites this paper as [127]

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Metadata

Authors
Shaked, I., Meerson, A., Wolf, Y., Avni, R., Greenberg, D., Gilboa-Geffen, A., & Soreq, H.
Venue
Immunity
Publisher
Elsevier BV
Published
2009-12
Volume
31
Issue
6
Pages
965-973
ISSN
1074-7613
DOI
10.1016/j.immuni.2009.09.019
Cited by
366
References
14
Language
en
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