Cytokines induce the expression and activity of cathepsin C in microglia in LPS-induced neuroinflamm

来源 :中国神经科学学会第九届全国学术会议暨第五届会员代表大会 | 被引量 : 0次 | 上传用户:jake9
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  Objective Neurodegenerative diseases accompany neuroinflammatory pathological process, during which injury or loss of neurons often occurs.As a result, cognition, learning or movement function is severely impaired.So far, the mechanism concerned is unclear.Cathepsin C (also called dipeptidyl peptidase, DPPI), a lysosomal cysteine protease, activates granule-associated serine proteases which play important roles in host reponses to bacterial infection in periphery tissues.However, whether cathepsin C participates in regulation of the process of inflammation in CNS remains unknown.The present study is to explore the role of cathepsin C in CNS inflammatory process.Methods An acute inflammation mice model was established by LPS (25 mg/kg, b.w.) intraperitoneally single injection.At different time points after LPS injection, the cellular localization, expression pattern and level of cathepsin C was detected by immunohistochemistry and Western blotting.The expression of Cathepsin C mRNA, IL-1β mRNA and TNFα mRNA were studied by in situ hybridization and RT-PCR.In vitro, BV2 mouse microglia lines were treated with various concentrations of LPS or IL-1β for 6 h.Then the expression of eathepsin C mRNA and the secretion of cathepsin C were detected by RT-PCR and ELISA, respectively.The activity of cathepsin C was measured by chromogenic substrate assay.Results After LPS injection, the expression of cathepsin C and cytokines in the brain was up-regulated.At 24 h point, the activated microglia started to express cathepsin C and its expression maintained at the highest level.In contrast, cathepsin C was exclusively expressed in neurons at 6 h point after LPS injection.In vitro, both cathepsin C mRNA expression and cathepsin C protein secretion were increased in LPS or IL-1β-treated BV2 cells in a dose-dependent manner.In addition, the activity of cathepsin C was also enhanced after treatment.Conclusion The results indicate that cytokines induce the expression and activity of cathepsin C in microglia in LPS-induced neuroinflammation, by which cathepsin C might participate in inflammatory processes in CNS.
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