Research ArticleSEPSIS

MEG3-4 is a miRNA decoy that regulates IL-1β abundance to initiate and then limit inflammation to prevent sepsis during lung infection

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Science Signaling  26 Jun 2018:
Vol. 11, Issue 536, eaao2387
DOI: 10.1126/scisignal.aao2387

Inflammatory decoy control

Inflammation resulting from bacterial infection can lead to sepsis and death if unresolved. The inflammatory response is dynamically regulated by long noncoding RNAs (lncRNAs). Li et al. examined tissue from mice intranasally infected with various bacterial strains and compared those with tissues from healthy controls. The lncRNA MEG3-4 and the mRNA encoding the proinflammatory cytokine IL-1β competitively bound to the microRNA miR-138 in the lungs. This facilitated bacterial infection–induced production of IL-1β, which activated pathways that reduced the abundance of MEG3-4 and increased that of miR-138, subsequently reducing IL-1β abundance and inflammatory signaling. Overexpressing MEG3-4 in the lungs exacerbated inflammation, prolonged infection, and enabled bacterial dissemination, which caused lung injury in mice, whereas intravenously delivering miR-138 mimics to infected mice enhanced their survival. These findings suggest how a feedback loop in the innate immune system may be manipulated to prevent lung injury and sepsis during pulmonary infection.

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