Objective: To investigate the regulatory effect of ATP?binding cassette transporter A1 (ABCA1) knockdown on inflammatory response induced by Pam3CSK4 in mouse mononuclear macrophage RAW264.7 cell line.
Methods: A mouse mononuclear macrophage RAW264.7 cell line with stable ABCA1 knockdown was constructed and stimulated with Toll?like receptor 2 (TLR2) ligand Pam3CSK4, and the changes in the transcriptional levels of the proinflammatory and anti-inflammatory cytokines were analyzed in this cell model.
Results: In RAW264.7 cells, ABCA1 knockdown significantly up-regulated Pam3CSK4 stimulation?induced expressions of IL?1β, TNF?α and IL?6 and also enhanced the expression of transcription factor cAMP?dependent transcription factor 3 (ATF3) without obviously affecting the expressions of the transcription factors ATF1, ATF2, ATF4 or ATF5.
Conclusion: ABCA1 knockdown in macrophages may have both proinflammatory and anti?inflammatory effects. ABCA1 knockdown up?regulates the transcription of ATF3 possibly through a mechanism that is different from that for the other members of the ATF protein family.
目的: 检测ABCA1敲低对巨噬细胞中Pam3CSK4引起的炎症应答的影响。
方法: 构建小鼠单核巨噬细胞RAW264.7的ABCA1敲低的稳定细胞系，以TLR2配体Pam3CSK4刺激该细胞系建立炎症反应细胞模型，在该细胞模型上检测相关促炎和抗炎细胞因子转录水平的表达变化。
结果: ABCA1敲低的RAW264.7稳定细胞株在Pam3CSK4刺激后，IL-1β，TNF-α和IL-6表达发生显著上调（P＜0.01），而转录抑制因子cAMP依赖性转录因子3（ATF3）也发生显著上调（P＜0.01）；与此同时，ATF蛋白家族中其它因子ATF1，ATF2，ATF4和ATF5转录水平没有发生显著变化。
结论: 在巨噬细胞RAW264.7中，ABCA1敲低显著上调Pam3CSK4引起的促炎因子IL-1β，TNF-α和IL-6的表达的同时，也显著上调了具有抗炎效应的ATF3的表达，其对炎症反应的影响可能并非是单向的促炎作用，而是发生双向的调节，而ABCA1参与上调ATF3表达的机制可能也与其ATF蛋白家族其他成员的上游调节机制不同。