title: 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.
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.
authors.affiliation: Department of Occupational and Environmental Medicine, West China School of Public Health, Sichuan University, Chengdu, Sichuan 610041, P.R. China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Occupational and Environmental Medicine, School of Public Health, Ningxia Medical University, Yinchuan, Ningxia 750004, P.R. China.
authors.forename: Faxuan
authors.initials: F
authors.lastname: Wang
authors.affiliation: Department of Occupational and Environmental Medicine, West China School of Public Health, Sichuan University, Chengdu, Sichuan 610041, P.R. China.
authors.forename: Yajia
authors.initials: Y
authors.lastname: Lan
authors.affiliation: Department of Occupational and Environmental Medicine, West China School of Public Health, Sichuan University, Chengdu, Sichuan 610041, P.R. China.
authors.forename: Dinglun
authors.initials: D
authors.lastname: Zhou
authors.affiliation: Department of Industrial Hygiene, 903 Hospital of China Academy of Engineering Physics, Mianyang, Sichuan 621900, P.R. China.
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Ren
authors.affiliation: Department of Occupational Disease, No. 4 West China Teaching Hospital, Sichuan University, Chengdu, Sichuan 610065, P.R. China.
authors.forename: Liqiang
authors.initials: L
authors.lastname: Zhao
authors.affiliation: Department of Occupational and Environmental Medicine, West China School of Public Health, Sichuan University, Chengdu, Sichuan 610041, P.R. China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Zhang
mesh_terms: D000818:Animals; D005786:Gene Expression Regulation; D053583:Interleukin-1beta / Q000235:genetics* / Q000378:metabolism; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D016676:Macrophages, Alveolar / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D035683:MicroRNAs / Q000819:agonists / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D009841:Oligonucleotides / Q000235:genetics / Q000378:metabolism; D061251:Primary Cell Culture; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D012822:Silicon Dioxide / Q000633:toxicity*; D012829:Silicosis / Q000209:etiology / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics* / Q000378:metabolism
chemical_list: D053583:Interleukin-1beta; C554180:MIRN146 microRNA, rat; C581717:MIRN181 microRNA, rat; D035683:MicroRNAs; D009841:Oligonucleotides; D014409:Tumor Necrosis Factor-alpha; D012822:Silicon Dioxide