Nurr1 Expression and Its Modulation in Microglia

• Published in: Neuroimmunomodulation 2009-01, Vol.16 (3), p.162-170
• Main Authors: Fan, Xiaolan, Luo, Guangrui, Ming, Ming, Pu, Pu, Li, Liang, Yang, Dehua, Le, Weidong
• Format: Article
• Language: English
• Subjects: Active Transport, Cell Nucleus - drug effects; Active Transport, Cell Nucleus - physiology; Animals; Animals, Newborn; Brain - cytology; Brain - metabolism; Cell Nucleus - metabolism; Cells, Cultured; Cytoplasm - metabolism; DNA-Binding Proteins - genetics; DNA-Binding Proteins - metabolism; Encephalitis - genetics; Encephalitis - metabolism; Encephalitis - physiopathology; Enzyme Inhibitors - pharmacology; Lipopolysaccharides - pharmacology; MAP Kinase Signaling System - drug effects; MAP Kinase Signaling System - physiology; Mice; Microglia - cytology; Microglia - metabolism; Nuclear Receptor Subfamily 4, Group A, Member 2; Original Paper; Parkinson Disease - genetics; Parkinson Disease - metabolism; Parkinson Disease - physiopathology; Phosphatidylinositol 3-Kinases - drug effects; Phosphatidylinositol 3-Kinases - metabolism; Protein Transport - drug effects; Protein Transport - physiology; Proto-Oncogene Proteins c-akt - drug effects; Proto-Oncogene Proteins c-akt - metabolism; Signal Transduction - physiology; Transcription Factors - genetics; Transcription Factors - metabolism; Up-Regulation - drug effects; Up-Regulation - physiology
• ISSN: 1021-7401; 1423-0216
• DOI: 10.1159/000204229

Objective:Nurr1, a transcription factor essential for the differentiation and maturation of central dopaminergic cells, is primarily expressed in neurons of the central nervous system. In this study, we intend to determine the expression and modulation of Nurr1 in cultured microglia. Methods: Nurr1 expression in cultured primary mouse microglia was measured by reverse transcription polymerase chain reaction, Western blot and immunofluorescent staining. Lipopolysaccharide (LPS) was used to activate microglia. Specific inhibitors were used to investigate whether the mitogen- activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK), MAPK/Jun N-terminal kinase (JNK), P38 MAPK and phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) pathways were involved in the modulation of Nurr1 expression.Results: Nurr1 was found to be located at both the cytoplasm and the nucleus of the microglia. After LPS stimulation, the expression of Nurr1 was significantly increased, which could be partially blocked by inhibitors of ERK, JNK and PI3K/Akt, but not by the P38 MAPK inhibitor; the ERK inhibitor can partially block the translocation of Nurr1 from the cytoplasm to the nucleus. Conclusion: Nurr1 is found to be expressed in cultured mouse microglia. The expression of Nurr1 is increased and the protein is translocated from the cytoplasm to the nucleus after activation by LPS, which could be modulated by the ERK, JNK and PI3K/Akt pathways.