RESUMO
OBJECTIVE: The dysregulation of neuro-inflammation is one of the attributes of the pathogenesis of Alzheimer's disease (AD). Over-expression of complement proteins co-localizes with neurofibrillary tangles, thereby indicating that a complement system may be involved in neuro-inflammation. Here, we report the influence of complement activation on the neuro-inflammation using a microglial cell line. METHODS: first, we performed a cytotoxic assay using the microglial cells BV-2. Second, after treatment of BV-2 cells with Aß42 and/ or C5a, the anaphylatoxin derived from C5, we determined the expression levels of the pro-inflammatory factors TNF-α, IL-1ß, and IL-6. Finally, we explored whether this neuroinflammatory response was mediated by JAK/ STAT3 signaling. RESULTS: C5a had an enhanced effect on the neural cell viability of BV-2 cells treated with Aß42. In addition, C5a also increased the Aß-induced neuro-inflammatory response, and these effects were blocked by the C5aR antagonist, PMX205. Finally, we demonstrated that the neuro-inflammatory responses induced by Aß and C5a were mediated through JAK/STAT3 signaling. By blocking this pathway with an antagonist, AG490, the expression of TNF-α, IL-1ß, and IL-6 was alleviated. CONCLUSION: The complement protein C5a could exaggerate the Aß-induced neuroinflammatory response in microglia, and C5aR may be a potential therapeutic tool for AD treatment.
