title: Peroxisome proliferator-activated receptor γ agonist troglitazone inhibits high mobility group box 1 expression in endothelial cells via suppressing transcriptional activity of nuclear factor κB and activator protein 1.
abstract: High mobility group box 1 (HMGB1), a delayed mediator of proinflammatory cytokines, could initiate and amplify inflammatory responses to infection, injury, and other inflammatory stimuli, and it has emerged as a potential therapeutic target for inflammatory diseases. The overexpression of HMGB1 in endothelial cells has been proved to contribute to the development of these diseases. Because many proinflammatory cytokines expression were suppressed by thiazolidinediones (TZDs), agonists for nuclear receptor peroxisome proliferator-activated receptor γ (PPARγ), whether TZDs can inhibit HMGB1 expression and function is of great interest, however, it remains unknown. Herein, we provide evidence that PPARγ agonist troglitazone, a member of the TZD class, modulates HMGB1 expression in the endothelial cell line EA.hy926 and propose a potential mechanism for that. Results from polymerase chain reaction experiments revealed that PPARγ is expressed in EA.hy926 cells, and it can be activated by troglitazone. Troglitazone inhibited the basal and LPS-stimulated HMGB1 expression at the mRNA level and protein level. A luciferase reporter assay showed that troglitazone inhibited not only the transcriptional activation of the HMGB1 promoter but also activities of heterologous promoters driven by nuclear factor κB (NF-κB) or activator protein 1 (AP-1) response elements. Altogether, these data suggest that NF-κB and AP-1 may participate in the inhibitory effect on HMGB1 transcription induced by troglitazone. Activation of PPARγ by troglitazone is effective for HMGB1 inhibition via suppressing NF-κB and AP-1 transcriptional activity in endothelial cells, which provides a new potential strategy to suppress excessive HMGB1 in inflammatory diseases.
authors: Department of Biochemistry and Molecular Biology, College of Basic Medical Sciences, Daping Hospital and Research Institute of Surgery, Third Military Medical University, Chongqing, PR China.
authors: Min
authors: M
authors: Gao
authors: Zhangxue
authors: Z
authors: Hu
authors: Yingru
authors: Y
authors: Zheng
authors: Yijun
authors: Y
authors: Zeng
authors: Xiaodong
authors: X
authors: Shen
authors: Dan
authors: D
authors: Zhong
authors: Fengtian
authors: F
authors: He