title: Troglitazone and Δ2Troglitazone enhance adiponectin expression in monocytes/macrophages through the AMP-activated protein kinase pathway.
abstract: Accumulating evidence indicates that the regimen to increase adiponectin will provide a novel therapeutic strategy for inflammation and cardiovascular disorders. Here, we tested the effect of troglitazone (TG) and its newly synthesized derivative, 5-[4-(6-hydroxy-2,5,7,8-tetramethyl-chroman-2-yl-methoxy)-benzylidene]-2,4-thiazolidinedione (Δ2troglitazone, (Δ2TG)), on the adiponectin expression in monocytes/macrophages and the relative mechanisms. The expression of adiponectin was located in macrophages of atherosclerotic lesions from patients and cholesterol-fed rabbits. TG and Δ2TG enhanced adiponectin mRNA and protein expression in THP-1 cells by quantitative real-time PCR, Western blot, and immunocytochemistry. TG induced adiponectin mRNA expression through a PPARγ-dependent pathway whereas Δ2TG enhanced adiponectin mRNA expression through a PPARγ-independent pathway in THP-1 cells. Both TG and Δ2TG enhanced adiponectin mRNA expression through AMP-activated protein kinase (AMPK) activation. TG and Δ2TG decreased the adhesion of THP-1 cells to TNF-α-treated HUVECs and the inhibitory effect was abolished by specific antiadiponectin antibodies. TG- and Δ2TG-induced suppression on monocyte adhesion were inhibited by a selective AMPK inhibitor compound C. Our data suggest that the inhibitory effect of TG and Δ2TG on monocyte adhesion might be at least in part through de novo adiponectin expression and activation of an AMPK-dependent pathway, which might play an important role in anti-inflammation and antiatherosclerosis.
authors.affiliation: Department of Family Medicine, College of Medicine, National Taiwan University, Taipei 10051, Taiwan.
authors.forename: Jaw-Shiun
authors.initials: JS
authors.lastname: Tsai
authors.affiliation: Department of Internal Medicine, College of Medicine, National Taiwan University, Taipei 10051, Taiwan.
authors.forename: Lee-Ming
authors.initials: LM
authors.lastname: Chuang
authors.affiliation: Division of Medicinal Chemistry, College of Pharmacy and Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210, USA ; Institute of Biological Chemistry, Academia Sinica, Taipei 11529, Taiwan.
authors.forename: Ching-Shih
authors.initials: CS
authors.lastname: Chen
authors.affiliation: Department of Anatomy and Cell Biology, College of Medicine, National Taiwan University, Taipei 10051, Taiwan.
authors.forename: Chan-Jung
authors.initials: CJ
authors.lastname: Liang
authors.affiliation: Department of Anatomy and Cell Biology, College of Medicine, National Taiwan University, Taipei 10051, Taiwan.
authors.forename: Yuh-Lien
authors.identifier: 0000-0002-6498-4008
authors.initials: YL
authors.lastname: Chen
authors.affiliation: Department of Family Medicine, College of Medicine, National Taiwan University, Taipei 10051, Taiwan ; Division of Geriatric Research, Institute of Population Health Science, National Health Research Institutes, Miaoli 35053, Taiwan.
authors.forename: Ching-Yu
authors.initials: CY
authors.lastname: Chen
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D052242:Adiponectin / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D050197:Atherosclerosis / Q000378:metabolism; D002448:Cell Adhesion / Q000187:drug effects; D002460:Cell Line; D002839:Chromans / Q000494:pharmacology*; D007150:Immunohistochemistry; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism*; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism*; D011817:Rabbits; D060888:Real-Time Polymerase Chain Reaction; D045162:Thiazolidinediones / Q000494:pharmacology*; D000077288:Troglitazone
chemical_list: D052242:Adiponectin; D002839:Chromans; D045162:Thiazolidinediones; D055372:AMP-Activated Protein Kinases; D000077288:Troglitazone