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http://purl.uniprot.org/citations/22607609http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/22607609http://www.w3.org/2000/01/rdf-schema#comment"

Background

Cathepsin C (Cat C) functions as a central coordinator for activation of many serine proteases in inflammatory cells. It has been recognized that Cat C is responsible for neutrophil recruitment and production of chemokines and cytokines in many inflammatory diseases. However, Cat C expression and its functional role in the brain under normal conditions or in neuroinflammatory processes remain unclear. Our previous study showed that Cat C promoted the progress of brain demyelination in cuprizone-treated mice. The present study further investigated the Cat C expression and activity in lipopolysaccharide (LPS)-induced neuroinflammation in vivo and in vitro.

Methods

C57BL/6 J mice were intraperitoneally injected with either 0.9% saline or lipopolysaccharide (LPS, 5 mg/kg). Immunohistochemistry (IHC) and in situ hybridization (ISH) were used to analyze microglial activation, TNF-α, IL-1β, IL-6, iNOS mRNAs expressions and cellular localization of Cat C in the brain. Nitrite assay was used to examine microglial activation in vitro; RT-PCR and ELISA were used to determine the expression and release of Cat C. Cat C activity was analyzed by cellular Cat C assay kit. Data were evaluated for statistical significance with paired t test.

Results

Cat C was predominantly expressed in hippocampal CA2 neurons in C57BL/6 J mice under normal conditions. Six hours after LPS injection, Cat C expression was detected in cerebral cortical neurons; whereas, twenty-four hours later, Cat C expression was captured in activated microglial cells throughout the entire brain. The duration of induced Cat C expression in neurons and in microglial cells was ten days and three days, respectively. In vitro, LPS, IL-1β and IL-6 treatments increased microglial Cat C expression in a dose-dependent manner and upregulated Cat C secretion and its activity.

Conclusions

Taken together, these data indicate that LPS and proinflammatory cytokines IL-1β, IL-6 induce the expression, release and upregulate enzymatic activity of Cat C in microglial cells. Further investigation is required to determine the functional role of Cat C in the progression of neuroinflammation, which may have implications for therapeutics for the prevention of neuroinflammation-involved neurological disorders in the future."xsd:string
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http://purl.uniprot.org/citations/22607609http://purl.uniprot.org/core/author"Fan B."xsd:string
http://purl.uniprot.org/citations/22607609http://purl.uniprot.org/core/author"Li N."xsd:string
http://purl.uniprot.org/citations/22607609http://purl.uniprot.org/core/author"Ma J."xsd:string
http://purl.uniprot.org/citations/22607609http://purl.uniprot.org/core/author"Lin Y."xsd:string
http://purl.uniprot.org/citations/22607609http://purl.uniprot.org/core/author"Wu X."xsd:string
http://purl.uniprot.org/citations/22607609http://purl.uniprot.org/core/author"Yao Y."xsd:string
http://purl.uniprot.org/citations/22607609http://purl.uniprot.org/core/author"Fan K."xsd:string
http://purl.uniprot.org/citations/22607609http://purl.uniprot.org/core/date"2012"xsd:gYear
http://purl.uniprot.org/citations/22607609http://purl.uniprot.org/core/name"J Neuroinflammation"xsd:string
http://purl.uniprot.org/citations/22607609http://purl.uniprot.org/core/pages"96"xsd:string
http://purl.uniprot.org/citations/22607609http://purl.uniprot.org/core/title"Up-regulation of microglial cathepsin C expression and activity in lipopolysaccharide-induced neuroinflammation."xsd:string
http://purl.uniprot.org/citations/22607609http://purl.uniprot.org/core/volume"9"xsd:string
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