title: Rosiglitazone inhibits monocyte/macrophage adhesion through de novo adiponectin production in human monocytes.
abstract: Rosiglitazone (RSG) has a variety of actions on both insulin sensitization and anti-atherogenic effects. The molecular effect of RSG on monocyte/macrophage function in terms of de novo synthesis of adiponectin is not fully understood. Here, we examined the regulation of adiponectin expression in human monocytes/macrophages by RSG and its function on monocyte adhesion during initiation of atherosclerosis. Adiponectin expression in monocytes and macrophages was studied by RT-PCR, quantitative real-time PCR, Western blot, and immunocytochemistry. Signal transduction and adhesion molecules were studied in order to describe the function of de novo synthesized adiponectin in monocyte adhesion. Adiponectin was expressed and upregulated during monocyte differentiation. The expression of adiponectin was enhanced, albeit at a much lesser degree, by a peroxisome proliferator-activated receptor gamma (PPAR gamma) agonist RSG, which was similar to what was found in adipocytes. Monocyte adhesion was remarkably reduced when the cells were treated with RSG for 12 h. This inhibitory effect of RSG was abolished by specific anti-adiponectin antibodies but not by non-immune immunoglobulin G in a serum-free condition. Adiponectin-induced suppression on monocyte adhesion was inhibited by a selective AMP-activated protein kinase (AMPK) inhibitor compound C. The reduced expression and/or function of adhesion molecule integrins may underlie the mechanism contributing to reduced monocyte adhesion upon AMPK activation. Our data suggest that the inhibitory effect of RSG 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 atherogenesis.
authors.affiliation: Graduate Institute of Clinical Medicine, National Taiwan University School of Medicine, Taipei, Taiwan.
authors.forename: Jaw-Shiun
authors.initials: JS
authors.lastname: Tsai
authors.forename: Ching-Yu
authors.initials: CY
authors.lastname: Chen
authors.forename: Yuh-Lien
authors.initials: YL
authors.lastname: Chen
authors.forename: Lee-Ming
authors.initials: LM
authors.lastname: Chuang
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D052242:Adiponectin / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D000620:Aminoimidazole Carboxamide / Q000031:analogs & derivatives / Q000494:pharmacology; D015153:Blotting, Western; D002448:Cell Adhesion / Q000187:drug effects; D002460:Cell Line; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007150:Immunohistochemistry; D008264:Macrophages / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D009000:Monocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D047495:PPAR gamma / Q000819:agonists / Q000235:genetics / Q000378:metabolism; D011720:Pyrazoles / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012265:Ribonucleotides / Q000494:pharmacology; D000077154:Rosiglitazone; D015398:Signal Transduction / Q000187:drug effects; D045162:Thiazolidinediones / Q000494:pharmacology*
chemical_list: D052242:Adiponectin; D047495:PPAR gamma; D011720:Pyrazoles; D011743:Pyrimidines; D012265:Ribonucleotides; D045162:Thiazolidinediones; D000077154:Rosiglitazone; C516138:dorsomorphin; D000620:Aminoimidazole Carboxamide; D055372:AMP-Activated Protein Kinases; C031143:AICA ribonucleotide