Activation of PPARγ inhibits pro-inflammatory cytokines production by upregulation of miR-124 in vitro and in vivo.
Peroxisome proliferator-activated receptor gamma (PPARγ) and miR-124 have been reported to play important roles in regulation of inflammation. However, the underlying anti-inflammatory mechanisms remain not well understood. In the present study, we demonstrated that the expression level of PPARγ is positively correlated with that of miR-124 in patients with sepsis. Activation of PPARγ upregulates miR-124 and in turn inhibits miR-124 target gene. PPARγ bound directly to PPRE in the miR-124 promoter region, and enhanced the promoter transcriptional activity. PPARγ-induced miR-124 is involved in the suppression of pro-inflammatory cytokine in vitro and in vivo. These results suggest that PPARγ-induced miR-124 inhibits the production of pro-inflammatory cytokines is a novel PPARγ anti-inflammatory mechanism and also indicate that miR-124 may be a potential therapeutic target for the treatment of inflammatory diseases.
Department of Respiratory Medicine, Respiratory Research Institute, The Second Affiliated Hospital, Third Military Medical University, Chongqing 400037, China.
Dan
D
Wang
Department of Scientific Research and Education, The Affiliated Baoji Hospital, Xi'an Medical University, Baoji 721006, China.
Liuyan
L
Shi
Department of Thoracic Surgery, Baoji Traditional Chinese Medicine Hospital, Baoji 721001, China.
Wei
W
Xin
Department of Respiratory Medicine, Respiratory Research Institute, The Second Affiliated Hospital, Third Military Medical University, Chongqing 400037, China.
Jiancheng
J
Xu
Department of Respiratory Medicine, Respiratory Research Institute, The Second Affiliated Hospital, Third Military Medical University, Chongqing 400037, China.
Jing
J
Xu
Department of Respiratory Medicine, Respiratory Research Institute, The Second Affiliated Hospital, Third Military Medical University, Chongqing 400037, China.
Qi
Q
Li
Department of Respiratory Medicine, Respiratory Research Institute, The Second Affiliated Hospital, Third Military Medical University, Chongqing 400037, China.
Zhi
Z
Xu
Department of Respiratory Medicine, Respiratory Research Institute, The Second Affiliated Hospital, Third Military Medical University, Chongqing 400037, China.
Jianchun
J
Wang
Department of Respiratory Medicine, Respiratory Research Institute, The Second Affiliated Hospital, Third Military Medical University, Chongqing 400037, China.
Guansong
G
Wang
Department of Respiratory Medicine, Respiratory Research Institute, The Second Affiliated Hospital, Third Military Medical University, Chongqing 400037, China.
Wei
W
Yao
Department of Respiratory Medicine, Respiratory Research Institute, The Second Affiliated Hospital, Third Military Medical University, Chongqing 400037, China.
Binfeng
B
He
Department of Respiratory Medicine, Respiratory Research Institute, The Second Affiliated Hospital, Third Military Medical University, Chongqing 400037, China.
Yu
Y
Yang
Department of Respiratory Medicine, Respiratory Research Institute, The Second Affiliated Hospital, Third Military Medical University, Chongqing 400037, China. Electronic address: humingdongxq@126.com.
Mingdong
M
Hu
D000818:Animals; D000070416:Antagomirs / Q000235:genetics / Q000378:metabolism; D001665:Binding Sites; D016022:Case-Control Studies; D002460:Cell Line; D005786:Gene Expression Regulation; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D035683:MicroRNAs / Q000819:agonists / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D047495:PPAR gamma / Q000235:genetics* / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D018805:Sepsis / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
D000070416:Antagomirs; D015850:Interleukin-6; D008070:Lipopolysaccharides; C509207:MIRN124 microRNA, human; D035683:MicroRNAs; D047495:PPAR gamma; D014409:Tumor Necrosis Factor-alpha; C577686:interleukin-6, mouse
Inflammation; Inflammatory cytokines; PPARγ; miR-124