title: MicroRNA-149 negatively regulates TLR-triggered inflammatory response in macrophages by targeting MyD88.
abstract: MicroRNAs (miRNAs) have been shown to be important regulators of TLR signaling pathway at the post-transcriptional level. In this study, the potential role of miR-149 was explored in murine alveolar macrophage RAW264.7 cells. Our results demonstrated a dynamic change of the expressions of miR-149 expression and MyD88 in macrophage RAW264.7 upon Mycobacterium bovis Bacillus Calmette-Guerlin (BCG) infection or lipopolysaccharide (LPS) stimulation. The presence of BCG or LPS dynamically reduced the miR-149 expression, along with a substantially striking increase of MyD88 expression in these cells. More importantly, overexpression of miR-149 in RAW264.7 cells was associated with a significant decrease of MyD88 protein expression, as well as a reduced production of inflammatory mediator NF-κB 1, TNF-α and IL-6 in response to BCG infection or LPS stimulation. Further studies using immunoblotting assay against anti-MyD88 antibody and microRNA targeting luciferase reporter assay revealed that miR-149 was able to directly target the 3'-UTR of MyD88 mRNA and post-transcriptionally regulated MyD88 protein expression. These data suggested that miR-149 might be a key player of immune modulator for TLR/MyD88 signaling pathway in macrophages, which may through a mechanism of negatively regulating MyD88-dependent Toll-like receptors signaling pathway.
authors.affiliation: General Hospital of Ningxia Medical University, Yinchuan, 750004, China; School of Laboratory Medicine, Ningxia Medical University, Yinchuan, 750004, China; Huashan Hospital, Fudan University, Shanghai, 200400, China.
authors.forename: Guangxian
authors.initials: G
authors.lastname: Xu
authors.forename: Zhaobo
authors.initials: Z
authors.lastname: Zhang
authors.forename: Yiwen
authors.initials: Y
authors.lastname: Xing
authors.forename: Jun
authors.initials: J
authors.lastname: Wei
authors.forename: Zhaohui
authors.initials: Z
authors.lastname: Ge
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Liu
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhang
authors.forename: Xuelan
authors.initials: X
authors.lastname: Huang
mesh_terms: D000818:Animals; D005786:Gene Expression Regulation / Q000235:genetics; D006801:Humans; D007249:Inflammation / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008070:Lipopolysaccharides / Q000633:toxicity; D008264:Macrophages / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D035683:MicroRNAs / Q000096:biosynthesis / Q000235:genetics*; D009163:Mycobacterium bovis / Q000472:pathogenicity; D053594:Myeloid Differentiation Factor 88 / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D051193:Toll-Like Receptors / Q000235:genetics / Q000378:metabolism
chemical_list: D008070:Lipopolysaccharides; C551557:MIRN149 microRNA, human; D035683:MicroRNAs; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D051193:Toll-Like Receptors
keywords: INFLAMMATORY RESPONSE; MyD88; TLR; microRNA-149