Tsai Jaw-Shiun, Chuang Lee-Ming, Chen Ching-Shih, Liang Chan-Jung, Chen Yuh-Lien, Chen Ching-Yu
Department of Family Medicine, College of Medicine, National Taiwan University, Taipei 10051, Taiwan.
Department of Internal Medicine, College of Medicine, National Taiwan University, Taipei 10051, Taiwan.
Mediators Inflamm. 2014;2014:726068. doi: 10.1155/2014/726068. Epub 2014 Sep 22.
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.
越来越多的证据表明，增加脂联素的治疗方案将为炎症和心血管疾病提供一种新的治疗策略。在此，我们测试了曲格列酮（TG）及其新合成的衍生物5-[4-(6-羟基-2,5,7,8-四甲基-色满-2-基-甲氧基)-亚苄基]-2,4-噻唑烷二酮（Δ2曲格列酮，(Δ2TG)）对单核细胞/巨噬细胞中脂联素表达的影响及其相关机制。脂联素的表达定位于患者和喂食胆固醇的兔子动脉粥样硬化病变的巨噬细胞中。通过定量实时PCR、蛋白质印迹和免疫细胞化学检测，TG和Δ2TG增强了THP-1细胞中脂联素mRNA和蛋白质的表达。在THP-1细胞中，TG通过PPARγ依赖性途径诱导脂联素mRNA表达，而Δ2TG通过PPARγ非依赖性途径增强脂联素mRNA表达。TG和Δ2TG均通过激活AMP激活的蛋白激酶（AMPK）增强脂联素mRNA表达。TG和Δ2TG降低了THP-1细胞与TNF-α处理的人脐静脉内皮细胞（HUVECs）的黏附，且特异性抗脂联素抗体消除了这种抑制作用。选择性AMPK抑制剂化合物C抑制了TG和Δ2TG诱导的对单核细胞黏附的抑制作用。我们的数据表明，TG和Δ2TG对单核细胞黏附的抑制作用可能至少部分是通过脂联素的从头表达和AMPK依赖性途径的激活，这可能在抗炎和抗动脉粥样硬化中起重要作用。
