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Published on: May 21, 2019
MicroRNA-127-5p attenuates severe pneumonia via tumor necrosis factor receptor-associated factor 1
Cunrong Chen1, Sen Lin2, Lili Zhou1
1Department of Critical Care Medicine, Union Hospital of Fujian Medical University, Fuzhou, Fujian 350111, P.R. China.
Abstract:
Pneumonia is a persistent and pervasive disease, the effects of which can be severe. MicroRNA (miR)-127-5p has been utilized as a novel biomarker for the diagnosis of severe pneumonia. The present study aimed to investigate the function of miR-127-5p during severe pneumonia. An in vitro model of severe pneumonia in Ana-1 murine macrophages was established using lipopolysaccharide (LPS). Subsequently, reverse transcription-quantitative PCR and ELISA were performed to detect the mRNA and protein expression levels of interleukin (IL)-1β, IL-6 and tumor necrosis factor (TNF)-α. Western blotting was also performed to measure the activity of AKT and NF-κB. The results indicated that compared with the control group, LPS treatment increased TNF receptor-associated factor 1 (TRAF1) expression levels and reduced miR-127-5p expression levels. Furthermore, the results revealed that the 3'-untranslated region of TRAF1 was targeted by miR-127-5p. miR-127-5p mimic reduced LPS-induced increases in IL-1β, IL-6 and TNF-α expression by targeting TRAF1, which was potentially mediated by inactivation of the AKT and NF-κB signaling pathways. Collectively, the results demonstrated that miR-127-5p may attenuate severe pneumonia by reducing LPS-induced inflammatory cytokine production, and inactivating the AKT and NF-κB signaling pathways by targeting TRAF1.
Insights
MicroRNA-127-5p may help treat severe pneumonia. This microRNA targets TRAF1, reducing inflammatory cytokine production and inactivating AKT and NF-κB pathways, potentially offering a new therapeutic strategy for pneumonia.
Area of Science:
- Molecular Biology
- Immunology
- Biochemistry
Background:
- Severe pneumonia remains a significant global health challenge.
- MicroRNA (miR)-127-5p shows promise as a diagnostic biomarker for severe pneumonia.
Purpose of the Study:
- To investigate the functional role of miR-127-5p in severe pneumonia.
- To elucidate the molecular mechanisms underlying miR-127-5p's action in pneumonia.
Main Methods:
- Established an in vitro severe pneumonia model using lipopolysaccharide (LPS) in murine macrophages.
- Utilized reverse transcription-quantitative PCR, ELISA, and Western blotting to assess gene and protein expression, and pathway activity.
- Investigated the interaction between miR-127-5p and TNF receptor-associated factor 1 (TRAF1).
Main Results:
- LPS treatment increased TRAF1 expression and decreased miR-127-5p levels.
- miR-127-5p directly targets the 3'-untranslated region of TRAF1.
- miR-127-5p mimic reduced LPS-induced inflammatory cytokine (IL-1β, IL-6, TNF-α) production.
- These effects were associated with the inactivation of AKT and NF-κB signaling pathways.
Conclusions:
- miR-127-5p plays a protective role in severe pneumonia.
- miR-127-5p attenuates inflammation by targeting TRAF1 and inhibiting AKT/NF-κB signaling.
- miR-127-5p represents a potential therapeutic target for severe pneumonia.
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