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Roles of microRNA-146a and microRNA-181b in regulating the secretion of tumor necrosis factor-α and interleukin-1β in silicon dioxide-induced NR8383 rat macrophages.

Zhang Y, Wang F, Lan Y, Zhou D, Ren X, Zhao L, Zhang Q - Mol Med Rep (2015)

Bottom Line: Analysis of variance and Student's two‑tailed t‑test were used to perform statistical analyses.The expression level of miR‑146a was significantly increased, while the expression level of miR‑181b was significantly decreased in the fibrotic lungs of the rats with silicosis, compared with the levels in the normal rats.By contrast, miR‑181b mimic transfection led to a significant reduction in the levels of TNF‑α (P<0.05), and miR‑146a mimics were responsible for the decrease in IL-1β (P<0.05).

View Article: PubMed Central - PubMed

Affiliation: Department of Occupational and Environmental Medicine, West China School of Public Health, Sichuan University, Chengdu, Sichuan 610041, P.R. China.

ABSTRACT
Despite increasing evidence to suggest that microRNA (miR)-146a and miR-181b are involved in the regulation of immune responses and tumor progression, their roles in silicosis remain to be fully elucidated. Therefore, the present study examined the roles of miR‑146a and miR‑181b in inflammatory responses, and their effect on the expression of the tumor necrosis factor‑α (TNF‑α) and interleukin‑1β (IL‑1β) inflammatory chemokines in silicon dioxide (SiO2)‑induced NR8383 rat macrophages. Alterations in the expression levels of miR‑146a and miR‑181b in rats with silicosis have been previously investigated using miRNA arrays. In the present study, the expression levels of miR‑146a and miR‑181b were assessed using reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR). The NR8383 cells were transfected with miRNA‑146a and miR‑181b mimics or inhibitors, and the cells and culture supernatants were collected following SiO2 treatment for 12 h. The expression levels of TNF‑α and IL‑1β were detected using western blotting, RT‑qPCR and ELISA. Analysis of variance and Student's two‑tailed t‑test were used to perform statistical analyses. The expression level of miR‑146a was significantly increased, while the expression level of miR‑181b was significantly decreased in the fibrotic lungs of the rats with silicosis, compared with the levels in the normal rats. It was observed that, following treatment of the NR8383 cells with SiO2 for 12 h, the levels of TNF‑α were significantly increased following miR‑181b knockdown and the levels of IL‑1β were significantly increased following miR‑146a knockdown, compared with the inhibitor‑treated controls (P<0.05). By contrast, miR‑181b mimic transfection led to a significant reduction in the levels of TNF‑α (P<0.05), and miR‑146a mimics were responsible for the decrease in IL-1β (P<0.05). The results of the present study provide evidence supporting the roles of miR‑146a and miR‑181b in the pathogenesis of silicosis, and suggest that they may be candidate therapeutic target in this disease.

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Expression levels of miR-146a and miR-181b in SiO2-treated lungs. miR, microRNA.
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f1-mmr-12-04-5587: Expression levels of miR-146a and miR-181b in SiO2-treated lungs. miR, microRNA.

Mentions: Typical fibrosis was observed in the SiO2-treated lungs, which involved infiltration of macrophages in alveolar spaces and increased collagen deposition (21). miRNA array analysis of the total RNA samples was performed on the day 40-SiO2-treated lungs, and these were compared with the respective controls, as described in our previous study (21). Of 1,890 miRNAs examined, 39 miRNAs were either up- or downregulated (P<0.05; fold changes >2) in the SiO2-treated lungs (21). In addition, the results of the RT-qPCR revealed that the expression of miR-146a was significantly increased and the expression of miR-181b was significantly decreased in the SiO2-treated lungs (Fig. 1).


Roles of microRNA-146a and microRNA-181b in regulating the secretion of tumor necrosis factor-α and interleukin-1β in silicon dioxide-induced NR8383 rat macrophages.

Zhang Y, Wang F, Lan Y, Zhou D, Ren X, Zhao L, Zhang Q - Mol Med Rep (2015)

Expression levels of miR-146a and miR-181b in SiO2-treated lungs. miR, microRNA.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4581828&req=5

f1-mmr-12-04-5587: Expression levels of miR-146a and miR-181b in SiO2-treated lungs. miR, microRNA.
Mentions: Typical fibrosis was observed in the SiO2-treated lungs, which involved infiltration of macrophages in alveolar spaces and increased collagen deposition (21). miRNA array analysis of the total RNA samples was performed on the day 40-SiO2-treated lungs, and these were compared with the respective controls, as described in our previous study (21). Of 1,890 miRNAs examined, 39 miRNAs were either up- or downregulated (P<0.05; fold changes >2) in the SiO2-treated lungs (21). In addition, the results of the RT-qPCR revealed that the expression of miR-146a was significantly increased and the expression of miR-181b was significantly decreased in the SiO2-treated lungs (Fig. 1).

Bottom Line: Analysis of variance and Student's two‑tailed t‑test were used to perform statistical analyses.The expression level of miR‑146a was significantly increased, while the expression level of miR‑181b was significantly decreased in the fibrotic lungs of the rats with silicosis, compared with the levels in the normal rats.By contrast, miR‑181b mimic transfection led to a significant reduction in the levels of TNF‑α (P<0.05), and miR‑146a mimics were responsible for the decrease in IL-1β (P<0.05).

View Article: PubMed Central - PubMed

Affiliation: Department of Occupational and Environmental Medicine, West China School of Public Health, Sichuan University, Chengdu, Sichuan 610041, P.R. China.

ABSTRACT
Despite increasing evidence to suggest that microRNA (miR)-146a and miR-181b are involved in the regulation of immune responses and tumor progression, their roles in silicosis remain to be fully elucidated. Therefore, the present study examined the roles of miR‑146a and miR‑181b in inflammatory responses, and their effect on the expression of the tumor necrosis factor‑α (TNF‑α) and interleukin‑1β (IL‑1β) inflammatory chemokines in silicon dioxide (SiO2)‑induced NR8383 rat macrophages. Alterations in the expression levels of miR‑146a and miR‑181b in rats with silicosis have been previously investigated using miRNA arrays. In the present study, the expression levels of miR‑146a and miR‑181b were assessed using reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR). The NR8383 cells were transfected with miRNA‑146a and miR‑181b mimics or inhibitors, and the cells and culture supernatants were collected following SiO2 treatment for 12 h. The expression levels of TNF‑α and IL‑1β were detected using western blotting, RT‑qPCR and ELISA. Analysis of variance and Student's two‑tailed t‑test were used to perform statistical analyses. The expression level of miR‑146a was significantly increased, while the expression level of miR‑181b was significantly decreased in the fibrotic lungs of the rats with silicosis, compared with the levels in the normal rats. It was observed that, following treatment of the NR8383 cells with SiO2 for 12 h, the levels of TNF‑α were significantly increased following miR‑181b knockdown and the levels of IL‑1β were significantly increased following miR‑146a knockdown, compared with the inhibitor‑treated controls (P<0.05). By contrast, miR‑181b mimic transfection led to a significant reduction in the levels of TNF‑α (P<0.05), and miR‑146a mimics were responsible for the decrease in IL-1β (P<0.05). The results of the present study provide evidence supporting the roles of miR‑146a and miR‑181b in the pathogenesis of silicosis, and suggest that they may be candidate therapeutic target in this disease.

Show MeSH
Related in: MedlinePlus