Rac1 Participates in Neuroinflammation Through Regulating JAK2/STAT1 Signaling Pathway
ZANG Cai-xia, LIU Hui, JU Cheng, YUAN Fang-yu, LI Fang-yuan, BAO Xiu-qi, ZHANG Dan*
State Key Laboratory of Natural Products and Functions, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China
Abstract：OBJECTIVE To investigate the role of Rac1 in neuroinflammation in BV2 microglia. METHODS Rac1 inhibitor EHT1864 was added to LPS-induced BV2 microglia, cell viability was detected by MTT assay, and Rac1 activity was detected by G-LISA and immunofluorescence. The production of ROS was detected by fluorescence microplate reader, the level of nitric oxide (NO) was detected by Griess reagent, and the release of tumor necrosis factor (TNF-α) and prostaglandin E2 (PGE2) was determined by enzyme-linked immunosorbent assay. Western blot was applied to detect the expressions of cyclooxygenase (COX-2) and inducible nitric oxide synthase (iNOS) to observe the neuroinflammatory response. RESULTS The activity of Rac1 and the inflammatory response were increased in LPS-induced BV2 cells, and Rac1 inhibitor EHT1864 inhibited inflammatory responses as decreasing the expression of inflammatory proteins (COX-2 and iNOS) and the release of inflammatory factors (ROS, NO, TNF-α and PGE2). Preliminary study found that EHT1864 inhibited the activation of Janus kinase 2 signal transducers and activators of transcription 1 (JAK2/STAT1) signaling pathway. CONCLUSION Rac1 participates in neuroinflammation through regulating JAK2/STAT1 signaling pathway in BV2 microglia.
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