Serum amyloid A stimulates lipoprotein-associated phospholipase A₂?expression in?vitro and in?vivo

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• 作者：Bo Li ; Zhe Dong ; Hui Liu ; Yan-fei Xia ; Xiao-man Liu ; Bei-bei Luo ; Wen-ke Wang ; Bin Li ; Fei Gao ; Cheng Zhang ; Ming-xiang Zhang ; Yun Zhang ; Feng-shuang An ; ^{anfengshuang@sina.com}
• 关键词：Lp-PLA2 ; SAA ; FPRL1 ; MAPK ; PPAR-¦Ã
• 刊名：Atherosclerosis
• 出版年：2013
• 出版时间：June, 2013
• 年：2013
• 卷：228
• 期：2
• 页码：370-379
• 全文大小：2503 K

文摘

Objectives

Although lipoprotein-associated phospholipase A₂ (Lp-PLA₂) has been regarded as a biomarker and a causative agent for acute coronary events recently, the mechanism of the regulation of Lp-PLA₂ has not been fully elucidated yet. This study was aimed to investigate the influence of serum amyloid A (SAA) on the expression of Lp-PLA₂ in THP-1 cells and ApoE-deficient (ApoE^?/?) mice.

Methods

THP-1 cells were stimulated by SAA and the mRNA and protein expression of Lp-PLA₂ was detected. ApoE^?/? mice were intravenously injected with murine SAA1 lentivirus. Formyl peptide receptor like-1 (FPRL1) agonist (WKYMVm) and inhibitor (WRW⁴), mitogen-activated protein kinases (MAPKs) inhibitors, and peroxisome proliferator-activated receptor-¦Ã (PPAR-¦Ã) agonist and inhibitor were used to investigate the mechanism of regulation of Lp-PLA₂.

Results

Recombinant SAA up-regulated Lp-PLA₂ expression in a dose and time-dependent manner in THP-1 cells. Immunohistochemical analysis of aortic root of ApoE^?/? mice also demonstrated that the expression of Lp-PLA₂ was up-regulated significantly with SAA treatment. WRW⁴ decreased SAA-induced Lp-PLA₂ production; while WKYMVm could induce Lp-PLA₂ expression. ERK1/2, JNK1/2, and p38 inhibition reduced SAA-induced Lp-PLA₂ production. Furthermore, the results suggested the activation of PPAR-¦Ã played a crucial role in this process.

Conclusion

These results demonstrate that SAA up-regulates Lp-PLA₂ production significantly via a FPRL1/MAPKs./PPAR-¦Ã signaling pathway.