Troglitazone and Δ2Troglitazone Enhance Adiponectin Expression in Monocytes/Macrophages through the AMP-Activated Protein Kinase Pathway

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-met...

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Main Authors: Jaw-Shiun Tsai, Lee-Ming Chuang, Ching-Shih Chen, Chan-Jung Liang, Yuh-Lien Chen, Ching-Yu Chen
Format: Article
Language:English
Published: Wiley 2014-01-01
Series:Mediators of Inflammation
Online Access:http://dx.doi.org/10.1155/2014/726068
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author Jaw-Shiun Tsai
Lee-Ming Chuang
Ching-Shih Chen
Chan-Jung Liang
Yuh-Lien Chen
Ching-Yu Chen
author_facet Jaw-Shiun Tsai
Lee-Ming Chuang
Ching-Shih Chen
Chan-Jung Liang
Yuh-Lien Chen
Ching-Yu Chen
author_sort Jaw-Shiun Tsai
collection DOAJ
description 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.
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spelling doaj-art-9393de5b09534093b6b0b396bf5318e72025-02-03T01:03:32ZengWileyMediators of Inflammation0962-93511466-18612014-01-01201410.1155/2014/726068726068Troglitazone and Δ2Troglitazone Enhance Adiponectin Expression in Monocytes/Macrophages through the AMP-Activated Protein Kinase PathwayJaw-Shiun Tsai0Lee-Ming Chuang1Ching-Shih Chen2Chan-Jung Liang3Yuh-Lien Chen4Ching-Yu Chen5Department of Family Medicine, College of Medicine, National Taiwan University, Taipei 10051, TaiwanDepartment of Internal Medicine, College of Medicine, National Taiwan University, Taipei 10051, TaiwanDivision of Medicinal Chemistry, College of Pharmacy and Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210, USADepartment of Anatomy and Cell Biology, College of Medicine, National Taiwan University, Taipei 10051, TaiwanDepartment of Anatomy and Cell Biology, College of Medicine, National Taiwan University, Taipei 10051, TaiwanDepartment of Family Medicine, College of Medicine, National Taiwan University, Taipei 10051, TaiwanAccumulating 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.http://dx.doi.org/10.1155/2014/726068
spellingShingle Jaw-Shiun Tsai
Lee-Ming Chuang
Ching-Shih Chen
Chan-Jung Liang
Yuh-Lien Chen
Ching-Yu Chen
Troglitazone and Δ2Troglitazone Enhance Adiponectin Expression in Monocytes/Macrophages through the AMP-Activated Protein Kinase Pathway
Mediators of Inflammation
title Troglitazone and Δ2Troglitazone Enhance Adiponectin Expression in Monocytes/Macrophages through the AMP-Activated Protein Kinase Pathway
title_full Troglitazone and Δ2Troglitazone Enhance Adiponectin Expression in Monocytes/Macrophages through the AMP-Activated Protein Kinase Pathway
title_fullStr Troglitazone and Δ2Troglitazone Enhance Adiponectin Expression in Monocytes/Macrophages through the AMP-Activated Protein Kinase Pathway
title_full_unstemmed Troglitazone and Δ2Troglitazone Enhance Adiponectin Expression in Monocytes/Macrophages through the AMP-Activated Protein Kinase Pathway
title_short Troglitazone and Δ2Troglitazone Enhance Adiponectin Expression in Monocytes/Macrophages through the AMP-Activated Protein Kinase Pathway
title_sort troglitazone and δ2troglitazone enhance adiponectin expression in monocytes macrophages through the amp activated protein kinase pathway
url http://dx.doi.org/10.1155/2014/726068
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