MicroRNA-146 inhibits pro-inflammatory cytokine secretion through IL-1 receptor-associated kinase 1 in human gingival fibroblasts

Journal of Inflammation

Research

Yu-Feng Xie¹  Jing Ni¹  Rong Shu¹  Da-Li Liu¹  Shao-Yun Jiang¹  Xiu-Li Zhang² 

[1] Department of Periodontology, Ninth People’s Hospital, School of Medicine Shanghai Jiao Tong University, Shanghai Key Laboratory of Stomatology, 639 Zhi Zao Ju Road, 200011, Shanghai, China;Shanghai Research Institute of Stomatology, Ninth People’s Hospital, School of Medicine Shanghai Jiao Tong University, Shanghai Key Laboratory of Stomatology, Shanghai, China;

关键词: miRNA-146;    Periodontitis;    Human gingival fibroblasts;    Pro-inflammatory cytokines;   

DOI  :  10.1186/1476-9255-10-20

 received in 2012-11-06, accepted in 2013-05-13,  发布年份 2013

来源: Springer

【 摘 要 】

BackgroundAlthough various microRNAs (miRNAs) regulate immune and inflammatory responses, the function of miRNAs in periodontitis has not been clearly illuminated. In this study, we measured miRNA-146 (miRNA-146a and miRNA-146b-5p) expression and explored its regulatory function in the inflammatory response in human gingival fibroblasts (HGFs).MethodsmiRNA-146a and miRNA-146b-5p expression was measured by performing real-time polymerase chain reaction in HGFs after Porphyromonas gingivalis (p.g) lipopolysaccharide (LPS) stimulation. After the HGFs were transfected with miRNA-146a and miRNA-146b-5p inhibitor, the expression levels of interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were measured by enzyme-linked immunosorbent assay (ELISA). Meanwhile, IL-1 receptor-associated kinase 1 (IRAK1) and TNF receptor-associated factor 6 (TRAF6) were detected by western blot and quantitative PCR. A luciferase assay was used to detect whether miRNA-146 could directly bind to the 3’-UTR of IRAK1.ResultsThe expression levels of miRNA-146a and miRNA-146b-5p significantly increased in the P.g LPS-stimulated HGFs compared to the non-stimulated HGFs. The inhibition of miRNA-146a and miRNA-146b-5p resulted in increased IL-1β, IL-6 and TNF-α secretion. The mRNA and protein levels of IRAK1, but not TRAF6, also increased. We further found that miRNA-146a and miRNA-146b-5p directly bound to the IRAK1 3’-UTR.ConclusionOur data suggest that miRNA-146 inhibits pro-inflammatory cytokine secretion through IRAK1 in HGFs, which indicates that miRNA-146 functions as a negative regulator of periodontal inflammation.

【 授权许可】

Unknown   
© Xie et al.; licensee BioMed Central Ltd. 2013. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.