Extracellular microRNA 130b-3p inhibits eCIRP-induced inflammation.


Journal

EMBO reports
ISSN: 1469-3178
Titre abrégé: EMBO Rep
Pays: England
ID NLM: 100963049

Informations de publication

Date de publication:
07 01 2020
Historique:
received: 12 03 2019
revised: 18 10 2019
accepted: 24 10 2019
pubmed: 15 11 2019
medline: 28 4 2021
entrez: 15 11 2019
Statut: ppublish

Résumé

Although microRNAs regulate mRNA expression intracellularly, they are often released into the circulation in inflammatory diseases. During sepsis, secreted extracellular cold-inducible RNA-binding protein (eCIRP) acts as a damage-associated molecular pattern (DAMP), inducing tissue damage by elevating inflammatory cytokines and chemokines. Here, we report that the circulating microRNA 130b-3p inhibits eCIRP-mediated sterile and cecal ligation and puncture (CLP)-induced non-sterile inflammation. We find that levels of miR-130b-3p are increased in the serum of septic mice and patients and that it strongly interacts with recombinant murine (rm) CIRP in vitro and with eCIRP in the serum of septic mice in vivo. Combining a miR-130b-3p mimic with rmCIRP significantly decreases TNF-α release by macrophages compared to only rmCIRP-treated cells. This combined treatment also dose-dependently decreases the affinity of rmCIRP with its receptor TLR4/MD2. Finally, injection of a miR-130b-3p mimic significantly reduces rmCIRP- or CLP-induced systemic inflammation and acute lung injury in mice. These data show that extracellular miR-130b-3p functions as a novel endogenous inhibitor of eCIRP and point to an innovative therapeutic approach to treat inflammatory diseases.

Identifiants

pubmed: 31724825
doi: 10.15252/embr.201948075
pmc: PMC10563445
doi:

Substances chimiques

Cytokines 0
MIRN130 microRNA, human 0
MIRN130 microRNA, mouse 0
MicroRNAs 0

Types de publication

Journal Article Research Support, N.I.H., Extramural

Langues

eng

Sous-ensembles de citation

IM

Pagination

e48075

Subventions

Organisme : NIGMS NIH HHS
ID : R01 GM129633
Pays : United States
Organisme : NIGMS NIH HHS
ID : R35 GM118337
Pays : United States

Commentaires et corrections

Type : CommentIn

Informations de copyright

© 2019 The Authors. Published under the terms of the CC BY 4.0 license.

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Auteurs

Steven D Gurien (SD)

Center for Immunology and Inflammation, The Feinstein Institutes for Medical Research, Manhasset, NY, USA.
Department of Surgery, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Manhasset, NY, USA.

Monowar Aziz (M)

Center for Immunology and Inflammation, The Feinstein Institutes for Medical Research, Manhasset, NY, USA.

Hui Jin (H)

Center for Immunology and Inflammation, The Feinstein Institutes for Medical Research, Manhasset, NY, USA.

Haichao Wang (H)

Center for Biomedical Science, The Feinstein Institutes for Medical Research, Manhasset, NY, USA.

Mingzhu He (M)

Center for Molecular Innovation, The Feinstein Institutes for Medical Research, Manhasset, NY, USA.

Yousef Al-Abed (Y)

Center for Molecular Innovation, The Feinstein Institutes for Medical Research, Manhasset, NY, USA.

Jeffrey M Nicastro (JM)

Department of Surgery, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Manhasset, NY, USA.

Gene F Coppa (GF)

Department of Surgery, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Manhasset, NY, USA.

Ping Wang (P)

Center for Immunology and Inflammation, The Feinstein Institutes for Medical Research, Manhasset, NY, USA.
Department of Surgery, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Manhasset, NY, USA.

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