MicroRNA-27a restrains the immune response to mycobacterium tuberculosis infection by targeting IRAK4, a promoter of the NF-κB pathway

• Published in: International journal of clinical and experimental pathology Vol. 10; no. 9; pp. 9894 - 9901
• Main Authors: Wang, Jianyun, Jia, Zhong, Wei, Baochu, Zhou, Yingquan, Niu, Chenxia, Bai, Shaoli, Tong, Chongxiang, Song, Juanjuan, Li, Yun
• Format: Journal Article
• Language: English
• Published: United States e-Century Publishing Corporation 01.01.2017
• Subjects: Original; MiR-27a; NF-κB; Mtb; immune response
• ISSN: 1936-2625

This study aimed to explore the influence of microRNA-27a on immune response to mycobacterium tuberculosis (Mtb) and the molecular mechanism. MiRNA-27a was screened one of the downregulated miRNAs in Mtb infected macrophages. The concentrations of IFN-γ, IL-β, IL-6, and TNF-α in THP-1 macrophages after infection with Mtb and simultaneous transfection with miR-27a mimics or inhibitor were determined by ELISA. Colony-forming unit (CFU) assay was used to determine the survival situation of THP-1 infected with Mtb after transfection with miR-27a mimics or inhibitor. We used luciferase reporter assay and western blotting to study the relationship between miR-27a and IRAK4. MiR-27a was found differential expressed in Mtb infected macrophages, and the expressions of miR-27a in Mtb-infected THP-1 were remarkably downregulated with the increase of time and dose. Compared with the control, the levels of IFN-γ, IL-β, IL-6, and TNF-α were enhanced after macrophages infected with Mtb, while further transfection of miR-27a mimics abolished the increase. IRAK4 was found the target gene of miR-27a and transfection of miR-27a mimics decreased the relative level of IRAK4. The concentration of IFN-γ, IL-β, IL-6, and TNF-α in Mtb infected macrophages were reduced significantly after transfection of miR-27a mimics, while simultaneous transfection of pcDNA-IRAK4 abolished the decrease, which is the upstream molecular of NF-κB. In conclusion, miR-27a plays a key role in immune response to Mtb infection and intervening on miR-27a may be an effective way to treat TB.