TRIM59 expression is regulated by Sp1 and Nrf1 in LPS-activated macrophages through JNK signaling pathway |
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| Institution: | 1. The First School of Clinical Medicine, Nanjing Medical University, Jiangsu Province, China;2. Hepatobiliary Center, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province, China;3. Key Laboratory of Liver Transplantation, Chinese Academy of Medical Sciences, Jiangsu Province, China;4. NHC Key Laboratory of Living Donor Liver Transplantation (Nanjing Medical University), Nanjing, Jiangsu Province, China;1. Department of Respiratory Medicine, XinHua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, China;2. State Key Laboratory of Microbial Metabolism, School of Life Science and Biotechnology, Shanghai Jiao Tong University, China;3. Department of Laboratory Medicine, XinHua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, China;4. Department of Immunology and Microbiology, Shanghai Jiao Tong University School of Medicine, China;5. Department of Pathology, XinHua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, China |
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| Abstract: | Activated macrophages play an important role in many inflammatory diseases including septic shock and atherosclerosis. TRIM59 has been showed to participate in many pathological processes, such as inflammation, cytotoxicity and tumorigenesis. However, the molecular mechanisms controlling its expression in activated macrophages are not fully understood. Here we report that TRIM59 expression is regulated by Sp1 and Nrf1 in LPS-activated macrophages. TRIM59 is highly expressed in macrophages, and markedly decreased by LPS stimuli in vivo and in vitro. TRIM59 promoter activity is also significantly suppressed by LPS and further analysis demonstrated that Sp1 and Nrf1 directly bound to the proximal promoter of TRIM59 gene. LPS treatment significantly decreased Sp1 expression, nuclear translocation and reduced its binding to the promoter, whereas increased Nrf1 expression, nuclear translocation and enhanced its binding to the promoter. Moreover, LPS-decreased TRIM59 expression was reversed by JNK inhibitor. Finally, TRIM59 level is significantly decreased during atherosclerosis progression. Taken together, our results demonstrated that TRIM59 expression was precisely regulated by Sp1 and Nrf1 in LPS-activated macrophages, which may be dependent on the activation of JNK signaling pathway and TRIM59 may be a potential therapeutic target for inflammatory diseases such as atherosclerosis. |
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