Abstract
Pneumonia is an inflammatory condition affecting the lungs, in which pro-inflammatory cytokines are secreted. It has been shown that microRNA-146 (miR-146) is involved in the regulation of immune and inflammatory responses. The present study explored the protective effects of miR-146 overexpression on lipopolysaccharide (LPS)-mediated injury in A549 and H1975 cells. In this study, A549 and H1975 cells were transfected with miR-146 mimic or inhibitor, and then were subjected with LPS. Thereafter, cell viability, colony formation capacity, apoptosis, the release of proinflammatory factors, Sirt1 expression, and the expression of NF-κB and Notch pathway proteins were respectively assessed. As a result, miR- 146 overexpression exerted protective functions on LPS-damaged A549 and H1975 cells, as evidenced by the increases in cell viability and colony number, the decrease in apoptotic cell rate, as well as the down-regulations of IL-1, IL-6, and TNF-α. Sirt1 can be positively regulated by miR-146. Furthermore, miR-146 overexpression blocked NF-κB and Notch pathways, while these blocking effects were abolished when Sirt1 was silenced. The findings in the current study indicated that miR-146 protected A549 and H1975 cells from LPS-induced apoptosis and inflammation injury. miR-146 exerted protective functions might be via up-regulation of Sirt1 and thereby blocking NF-κB and Notch pathways.
MeSH terms
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A549 Cells
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Antagomirs / genetics
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Antagomirs / metabolism
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Apoptosis / drug effects
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Cell Line, Tumor
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Cell Survival / drug effects
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Gene Expression Regulation
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Humans
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Interleukin-1 / antagonists & inhibitors
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Interleukin-1 / genetics
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Interleukin-1 / metabolism
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Interleukin-6 / antagonists & inhibitors
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Interleukin-6 / genetics
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Interleukin-6 / metabolism
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Lipopolysaccharides / antagonists & inhibitors
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Lipopolysaccharides / pharmacology*
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MicroRNAs / antagonists & inhibitors
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MicroRNAs / genetics*
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MicroRNAs / metabolism
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Molecular Mimicry
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NF-kappa B / antagonists & inhibitors
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NF-kappa B / genetics*
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NF-kappa B / metabolism
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Oligonucleotides / genetics
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Oligonucleotides / metabolism
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Plasmids / chemistry
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Plasmids / metabolism
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RNA, Small Interfering / genetics
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RNA, Small Interfering / metabolism
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Receptors, Notch / antagonists & inhibitors
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Receptors, Notch / genetics*
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Receptors, Notch / metabolism
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Signal Transduction
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Sirtuin 1 / antagonists & inhibitors
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Sirtuin 1 / genetics*
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Sirtuin 1 / metabolism
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Transfection
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Tumor Necrosis Factor-alpha / antagonists & inhibitors
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Tumor Necrosis Factor-alpha / genetics
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Tumor Necrosis Factor-alpha / metabolism
Substances
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Antagomirs
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IL6 protein, human
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Interleukin-1
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Interleukin-6
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Lipopolysaccharides
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MIRN146 microRNA, human
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MicroRNAs
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NF-kappa B
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Oligonucleotides
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RNA, Small Interfering
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Receptors, Notch
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Tumor Necrosis Factor-alpha
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SIRT1 protein, human
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Sirtuin 1