miR-146a in PBMCs modulates Th1 function in patients with acute coronary syndrome.
The upregulation of Th1 cells has been suggested to have an essential function in the development of atherosclerosis (AS). Recent studies indicate that miR-146a is a microRNA specifically and highly expressed in Th1-driven autoimmune disease. The aim of the study was to investigate the possible mechanisms of the miR-146a in the onset of acute coronary syndrome (ACS). The results showed that the expression of miR-146a in peripheral blood mononuclear cells (PBMCs) was significantly increased in patients with ACS. We showed that overexpression of miR-146a in PBMCs could significantly upregulate the function of Th1 cells. Furthermore, we showed that miR-146a treatment could modulate the Th1 differentiation through posttranscriptional enhancing the T-bet pathway in PBMCs. In addition, this study also provided evidence that miR-146a treatment in vitro could induce the protein expression of TNF-alpha, MCP-1, NF-kappaB p65, which are key pro-inflammatory cytokines and critical transcription factor in AS. In contrast, miR-146a inhibitor could attenuate these phenomena significantly. The results support the concept that miR-146a may be a novel regulatory factor in Th1 differentiation and a new therapeutic target for AS and ACS.
Guo
Min
M
Department of Cardiology, Institute of Cardiovascular Disease, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Mao
Xiaobo
X
Ji
Qingwei
Q
Lang
Mingjian
M
Li
Songnan
S
Peng
Yudong
Y
Zhou
Wei
W
Xiong
Bo
B
Zeng
Qiutang
Q
D054058:Acute Coronary Syndrome / Q000209:etiology / Q000235:genetics / Q000276:immunology*; D050197:Atherosclerosis / Q000150:complications / Q000235:genetics / Q000276:immunology*; D015153:Blotting, Western; D002454:Cell Differentiation / Q000276:immunology; D002469:Cell Separation; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000276:immunology*; D008297:Male; D035683:MicroRNAs / Q000276:immunology*; D008875:Middle Aged; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000276:immunology; D018417:Th1 Cells / Q000166:cytology / Q000276:immunology*
D016207:Cytokines; C542542:MIRN146 microRNA, human; D035683:MicroRNAs