[The roles of C5a and C5aR antagonist in TNF-α secretion and CD88 expression of BV2 microglial cells treated with Aβ1-42 oligomer].

Objective: To investigate the role of C5a in the release of TNF-α from microglial cells and its related mechanism, and identify the intervention effect of C5aR antagonist (C5aRA) in the pathological change of Alzheimer's disease (AD).
Methods: Soluble Aβ1-42 oligomer was prepared, identified by atomic force microscopy. Then Aβ1-42 oligomer alone, or in a combination with different levels of C5a, C5aRA, or C5a+C5aRA was used to treat cultured BV2 cells. The non-treated BV2 cells served as controls. ELISA was used to detect the concentration of TNF-α, and flow cytometry to analyze the expression of C5a receptor (CD88).
Results: Aβ1-42 oligomer significantly stimulated BV2 cells to release TNF-α and CD88, compared to the control group (P<0.05 and P<0.01, respectively). C5a further increased the release of TNF-α (P<0.05 vs Aβ1-42 group). In contrast, C5aRA inhibited remarkably the release of TNF-α stimulated by Aβ1-42 (P<0.01). Nevertheless, C5a or C5aRA didn't show a significant effect on the expression of CD88 in BV2 cells that was elevated by Aβ1-42 treatment (P>0.05).
Conclusion: C5a promotes the release of TNF-α from microglial cells; Aβ1-42 can further boost the release and C5aRA can inhibite TNF-α secretion of microglial cells significantly.