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Published on: April 10, 2018
LncRNA MALAT1 Affects Mycoplasma pneumoniae Pneumonia via NF-κB Regulation
Haiyan Gu1, Yifan Zhu1, Yao Zhou1
1Department of Respiratory Medicine, Children's Hospital of Nanjing Medical University, Nanjing, China.
Abstract:
Our aim was to determine whether the long non-coding RNA (lncRNA) metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is involved in Mycoplasma pneumoniae pneumonia (MPP), and its possible mechanism of action. MALAT1 expression in the bronchoalveolar lavage fluid of 50 hospitalized children with MPP was compared to its expression in 30 children with intrabronchial foreign bodies. MALAT1 expression was higher in children with MPP, accompanied by increased inflammatory mediators interleukin 8 (IL-8) and tumor necrosis factor alpha (TNF-α), compared to the controls. In human airway epithelial cells infected with wild-type Mycoplasma pneumoniae (strain M129), MALAT1, IL-8, and TNF-α expression significantly increased, and increased expression of IL-8 and TNF-α could be suppressed by MALAT1 knockdown. Luciferase reporter gene assay and western blot showed that knockdown of MALAT1 reduced nuclear factor-κB (NF-κB) activation. In vivo, RNAi packaged with adenovirus (Adv) was nasally transfected into BALB/c mice to silence MALAT1, and an MP-infected mouse pneumonia model was prepared. The results demonstrated that the degree of pulmonary inflammatory injury, vascular permeability, secretion of inflammatory factors, and expression of phosphorylated p65 (pp65) in MP-infected mice were partly reversed after MALAT1 knockdown compared to those in the controls. In conclusion, MALAT1 is involved in the regulation of airway and pulmonary inflammation caused by MP infection via NF-κB regulation.
Insights
The long non-coding RNA MALAT1 is elevated in Mycoplasma pneumoniae pneumonia (MPP) and drives inflammation by activating the NF-κB pathway. Silencing MALAT1 reduces inflammatory responses in both cell and mouse models of MPP.
Area of Science:
- Molecular Biology
- Immunology
- Respiratory Medicine
Background:
- Mycoplasma pneumoniae pneumonia (MPP) is a common respiratory infection.
- The role of long non-coding RNAs (lncRNAs) in MPP pathogenesis is not fully understood.
- Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is a lncRNA implicated in various cellular processes.
Purpose of the Study:
- To investigate the involvement of MALAT1 in MPP.
- To elucidate the underlying mechanism of MALAT1's action in MPP.
- To assess the therapeutic potential of targeting MALAT1 in MPP.
Main Methods:
- Comparison of MALAT1 expression in bronchoalveolar lavage fluid from children with MPP versus controls.
- In vitro studies using human airway epithelial cells infected with Mycoplasma pneumoniae, involving MALAT1 knockdown.
- In vivo studies using a mouse model of MP pneumonia with MALAT1 silencing via adenovirus-mediated RNAi.
Main Results:
- MALAT1 expression was significantly higher in children with MPP, correlating with increased inflammatory mediators IL-8 and TNF-α.
- MALAT1 knockdown suppressed IL-8 and TNF-α expression and reduced NF-κB activation in vitro.
- MALAT1 silencing in vivo partially reversed pulmonary inflammation, vascular permeability, and inflammatory factor secretion in MP-infected mice.
Conclusions:
- MALAT1 plays a significant role in regulating airway and pulmonary inflammation during Mycoplasma pneumoniae infection.
- The mechanism involves the regulation of the NF-κB signaling pathway.
- MALAT1 represents a potential therapeutic target for managing MPP.
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