The functional role of cathepsin C expression in microglia in LPS induced neuroinflammation

来源 :第九届海内外华人神经科学家研讨会(The 9th Symposium for Chinese Neuroscientis | 被引量 : 0次 | 上传用户:wxlcc1026
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  Neuroinflammation characterized by increased activation of glial cells,immune cells infiltration and inflammatory cytokines release,is the common pathological feature of diseases in the central nervous system(CNS).Microglia(MG)as antigen-presenting and innate immune cells in the CNS plays an important role in neuroinflammation by polarized into M1 and M2 phenotypes which have very different morphology and functions.Cathepsin C(Cat C)belongs to papain hydrolase supper family and has been found involved in peripheral inflammatory disease by which regulates the activation of serine proteases in T cells,natural killer cells,neutrophils and mast cells,but the functional role of Cat C in the CNS neuroinflammation is unclear.In present study,we used microglial Cat C conditional knock down(KD)and overexpression(OE)mice to create neuroinflammatory animal model by LPS intraperitoneal or intraventricular injection.In vitro,primary MG which isolated from Cat C KD and OE mice were cultured and stimulated by LPS.Then the morphological changes of microglia and the expression of proinflammatory cytokines were detected by IHC,in situ hybridization and ELISA.Furthermore,recombinant active Cat C was used to stimulate primary cultured MG that from wild type mice,then flow cytometry and RT-PCR were performed to detect MG polarization by using M1 and M2 markers.We found that Cat C could increase expression and release of proinflammatory cytokines TNF-α and IL-1β in activated microglia,and these may be caused by promoting microglia polarized into M1 phenotype.
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