Med Sci (Paris)
Volume 34, October 2018Cancer biomarkers
|Page(s)||116 - 120|
|Published online||07 November 2018|
Complement protein C5a enhances the β-amyloid-induced neuro-inflammatory response in microglia in Alzheimer’s disease
MD, Department of Psychiatry, Yangpu District Mental Health Center of Shanghai, 585 Jungong Road, Shanghai (200090), China
2 MD, Department of Psychological Medicine, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai (200032), China
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 Aβ42 and/ or C5a, the anaphylatoxin derived from C5, we determined the expression levels of the pro-inflammatory factors TNF-α, IL-1β, 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 Aβ42. In addition, C5a also increased the Aβ-induced neuro-inflammatory response, and these effects were blocked by the C5aR antagonist, PMX205. Finally, we demonstrated that the neuro-inflammatory responses induced by Aβ and C5a were mediated through JAK/STAT3 signaling. By blocking this pathway with an antagonist, AG490, the expression of TNF-α, IL-1β, and IL-6 was alleviated.
Conclusion: The complement protein C5a could exaggerate the Aβ-induced neuroinflammatory response in microglia, and C5aR may be a potential therapeutic tool for AD treatment.
Key words: Alzheimer’s disease / β-amyloid / complement system / neuro-inflammatory response / STAT3
The authors contributed equally to this work. They are co-corresponding authors email@example.com firstname.lastname@example.org
© 2018 médecine/sciences – Inserm
Current usage metrics show cumulative count of Article Views (full-text article views including HTML views, PDF and ePub downloads, according to the available data) and Abstracts Views on Vision4Press platform.
Data correspond to usage on the plateform after 2015. The current usage metrics is available 48-96 hours after online publication and is updated daily on week days.
Initial download of the metrics may take a while.