MicroRNA‑17 contributes to the suppression of the inflammatory response in lipopolysaccharide‑induced acute lung injury in mice via targeting the toll‑like receptor 4/nuclear factor‑κB pathway

Fu,Shan

doi:10.3892/ijmm.2020.4599

MicroRNA‑17 contributes to the suppression of the inflammatory response in lipopolysaccharide‑induced acute lung injury in mice via targeting the toll‑like receptor 4/nuclear factor‑κB pathway

Authors:
- Shan Fu
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Affiliations: Department of Emergency, Affiliated Hospital of Inner Mongolia University for Nationalities, Tongliao, Inner Mongolia 028000, P.R. China
Published online on: May 12, 2020 https://doi.org/10.3892/ijmm.2020.4599
Pages: 131-140
Copyright: © Fu . This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Acute lung injury (ALI) is a common lung disease with a high mortality rate, which is characterized by an excessive uncontrolled inflammatory response. MicroRNA (miR)‑17 has previously emerged as a novel regulatory molecule of inflammatory response in various complex diseases; however, the anti‑inflammatory action and associated molecular mechanisms of miR‑17 in ALI have not been fully elucidated. The aim of the present study was to investigate the role of miR‑17 in the inflammatory response in ALI and to elucidate the potential underlying mechanism. Using a lipopolysaccharide (LPS)‑induced ALI mouse model, it was observed that miR‑17 was significantly downregulated in lung tissues compared with the control group. In this model, ectopic expression of miR‑17 attenuated lung pathological damage, reduced lung wet/dry ratio and lung permeability, and increased survival rate in ALI mice. In addition, agomiR‑17 injection significantly suppressed LPS‑induced inflammation, as evidenced by a reduction in the activity of myeloperoxidase and the production of interleukin (IL)‑6, IL‑1β and tumor necrosis factor‑α in lung tissues. Of note, toll‑like receptor (TLR) 4, an upstream regulator of the nuclear factor (NF)‑κB inflammatory signaling pathway, was directly targeted by miR‑17, and its translation was suppressed by miR‑17 in vitro and in vivo. Using an LPS‑induced RAW264.1 macrophage injury model, it was observed that miR‑17 overexpression suppressed the pro‑inflammatory effect of LPS, while these inhibitory effects were markedly abrogated by TLR4 overexpression. In addition, TLR4 knockdown by si‑TLR4 mimicked the effects of miR‑17 overexpression on LPS‑induced cytokine secretion in the in vitro model. Further experiments revealed that miR‑17 significantly reduced the expression of key proteins in the NF‑κB pathway, including IKKβ, p‑IκBα and nuclear p‑p65, and suppressed the NF‑κB activity in ALI mice. Collectively, these results indicated that miR‑17 protected mice against LPS‑induced lung injury via inhibiting inﬂammation by targeting the TLR4/NF‑κB pathway; therefore, miR‑17 may serve as a potential therapeutic target for ALI.

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