title: miR-146a-5p Antagonized AGEs- and P.g-LPS-Induced ABCA1 and ABCG1 Dysregulation in Macrophages via IRAK-1 Downregulation.
abstract: The miR-146-mediated IL-1 receptor-associated kinase 1 (IRAK-1) feedback circuit has been shown to inhibit inflammatory response in macrophages against lipopolysaccharide (LPS). The aim of this study is to compare the antagonized effects of miR-146a-5p on Porphyromonas gingivalis (P.g) lipolysaccharide (LPS)- and advanced glycation end products (AGEs)-triggered ABCA1 and ABCG1 dysregulation and explore the underlying mechanism. THP-1-derived macrophages transfected with miRNA mimics or not were treated with P.g LPS or AGE-BSA, respectively. The mechanism of endotoxin tolerance was mimicked. miR-146a-5p levels and protein levels of IRAK-1, LXRα/β, ABCA1, and ABCG1 were detected by stem-loop reverse transcription followed by TaqMan PCR analysis and Western blotting. Our results showed that miR-146a-5p levels were significantly increased in macrophages after 24 h of stimulation with high dose of P.g LPS or AGE-BSA. Macrophages transfected with miR-146a-5p mimics attenuated the dysregulation of ABCA1/G1 induced by P.g LPS and AGEs through IRAK-1 downregulation. In low-dose LPS-tolerized cells, elevated miR-146a-5p antagonized the increase of ABCA1, ABCG1, and IRAK-1. However, low-dose AGE-BSA did not increase miR-146a-5p levels. In conclusion, the model of endotoxin tolerance is suitable for the antagonistic effects on the dysregulation of ABCA1/G1 induced by high dose of P.g LPS. Conversely, low-dose AGEs did not induce the model of P.g LPS-mediated tolerance.
authors: Department of Internal Medicine, Hebei Medical University, No.361 Zhongshan East Road, Shijiazhuang, Hebei, 050017, People's Republic of China.
authors: Xia
authors: X
authors: Li
authors: Zheng
authors: Z
authors: Ji
authors: Si
authors: S
authors: Li
authors: Ya-Nan
authors: YN
authors: Sun
authors: Jia
authors: J
authors: Liu
authors: Ying
authors: Y
authors: Liu
authors: Wei
authors: W
authors: Tian
authors: Yun-Tao
authors: YT
authors: Zhou
authors: Xiao-Ming
authors: XM
authors: Shang
mesh_terms: D064286:ATP Binding Cassette Transporter 1 / Q000096:biosynthesis*; D000070998:ATP Binding Cassette Transporter, Subfamily G, Member 1; D018528:ATP-Binding Cassette Transporters / Q000096:biosynthesis*; D000818:Animals; D002417:Cattle; D002460:Cell Line; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology; D017127:Glycation End Products, Advanced / Q000633:toxicity*; D006801:Humans; D053592:Interleukin-1 Receptor-Associated Kinases / Q000096:biosynthesis*; D008070:Lipopolysaccharides / Q000633:toxicity; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D016966:Porphyromonas gingivalis; D012710:Serum Albumin, Bovine / Q000633:toxicity
chemical_list: C577836:ABCA1 protein, human; C419353:ABCG1 protein, human; D064286:ATP Binding Cassette Transporter 1; D000070998:ATP Binding Cassette Transporter, Subfamily G, Member 1; D018528:ATP-Binding Cassette Transporters; D017127:Glycation End Products, Advanced; D008070:Lipopolysaccharides; C542542:MIRN146 microRNA, human; D035683:MicroRNAs; D012710:Serum Albumin, Bovine; C507768:IRAK1 protein, human; D053592:Interleukin-1 Receptor-Associated Kinases