TLR7 Mediates Acute Respiratory Distress Syndrome in Sepsis by Sensing Extracellular miR-146a.
Toll-like receptors
acute respiratory distress syndrome
innate immunity
microRNAs
sepsis
Journal
American journal of respiratory cell and molecular biology
ISSN: 1535-4989
Titre abrégé: Am J Respir Cell Mol Biol
Pays: United States
ID NLM: 8917225
Informations de publication
Date de publication:
09 2022
09 2022
Historique:
pubmed:
10
6
2022
medline:
9
9
2022
entrez:
9
6
2022
Statut:
ppublish
Résumé
TLR7 (Toll-like receptor 7), the sensor for single-stranded RNA, contributes to systemic inflammation and mortality in murine polymicrobial sepsis. Recent studies show that extracellular miR-146a-5p serves as a TLR7 ligand and plays an important role in regulating host innate immunity. However, the role of miR-146a-5p and TLR7 signaling in pulmonary inflammation, endothelial activation, and sepsis-associated acute respiratory distress syndrome remains unclear. Here, we show that intratracheal administration of exogenous miR-146a-5p in mice evokes lung inflammation, activates endothelium, and increases endothelial permeability via TLR7-dependent mechanisms. TLR7 deficiency attenuates pulmonary barrier dysfunction and reduces lung inflammatory response in a murine sepsis model. Moreover, the impact of miR-146a-5p-TLR7 signaling on endothelial activation appears to be a secondary effect because TLR7 is undetectable in the human pulmonary artery and microvascular endothelial cells (ECs), which show no response to direct miR-146a-5p treatment
Identifiants
pubmed: 35679261
doi: 10.1165/rcmb.2021-0551OC
pmc: PMC9447138
doi:
Substances chimiques
Culture Media, Conditioned
0
Membrane Glycoproteins
0
MicroRNAs
0
Mirn146 microRNA, mouse
0
Tlr7 protein, mouse
0
Toll-Like Receptor 7
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
375-388Subventions
Organisme : NIGMS NIH HHS
ID : R35 GM124775
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS110567
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL076259
Pays : United States
Organisme : NIGMS NIH HHS
ID : R35 GM140822
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL146829
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL152761
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL155051
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM117233
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM122908
Pays : United States
Commentaires et corrections
Type : CommentIn
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