title: [The roles of C5a and C5aR antagonist in TNF-α secretion and CD88 expression of BV2 microglial cells treated with Aβ1-42 oligomer].
abstract: 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).
  
  
  CONCLUSIONS
  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.
authors: Department of Neurology, Guangdong Institute for Geriatrics, Guangzhou, China.
authors: Fan
authors: F
authors: Yang
authors: Dongfeng
authors: D
authors: Li
authors: Shuwen
authors: S
authors: Xu
mesh_terms: D016229:Amyloid beta-Peptides / Q000737:chemistry* / Q000494:pharmacology*; D000818:Animals; D002460:Cell Line; D015936:Complement C5a / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D051379:Mice; D017628:Microglia / Q000166:cytology*; D010446:Peptide Fragments / Q000737:chemistry* / Q000494:pharmacology*; D010456:Peptides, Cyclic / Q000494:pharmacology; D055503:Protein Multimerization; D017433:Protein Structure, Secondary; D044087:Receptor, Anaphylatoxin C5a / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; D010456:Peptides, Cyclic; D044087:Receptor, Anaphylatoxin C5a; D014409:Tumor Necrosis Factor-alpha; C075222:amyloid beta-protein (1-42); C504156:hydrocinnamate-cyclo(ornithyl-prolyl-cyclohexylalanyl-tryptophyl-arginyl); D015936:Complement C5a