Up-regulation of microglial cathepsin C expression and activity in lipopolysaccharide-induced neuroinflammation

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. © 2012 fan et al.; licensee biomed central ltd.