title: Serum amyloid A stimulates lipoprotein-associated phospholipase A2 expression in vitro and in vivo.
abstract: OBJECTIVE
  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 (WRW(4)), mitogen-activated protein kinases (MAPKs) inhibitors, and peroxisome proliferator-activated receptor-γ (PPAR-γ) 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. WRW(4) 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-γ played a crucial role in this process.
  
  
  CONCLUSIONS
  These results demonstrate that SAA up-regulates Lp-PLA2 production significantly via a FPRL1/MAPKs./PPAR-γ signaling pathway.
authors.affiliation: Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese Ministry of Public Health, Department of Cardiology, Qilu Hospital of Shandong University, Ji'nan 250012, PR China.
authors.forename: Bo
authors.initials: B
authors.lastname: Li
authors.forename: Zhe
authors.initials: Z
authors.lastname: Dong
authors.forename: Hui
authors.initials: H
authors.lastname: Liu
authors.forename: Yan-Fei
authors.initials: YF
authors.lastname: Xia
authors.forename: Xiao-Man
authors.initials: XM
authors.lastname: Liu
authors.forename: Bei-Bei
authors.initials: BB
authors.lastname: Luo
authors.forename: Wen-Ke
authors.initials: WK
authors.lastname: Wang
authors.forename: Bin
authors.initials: B
authors.lastname: Li
authors.forename: Fei
authors.initials: F
authors.lastname: Gao
authors.forename: Cheng
authors.initials: C
authors.lastname: Zhang
authors.forename: Ming-Xiang
authors.initials: MX
authors.lastname: Zhang
authors.forename: Yun
authors.initials: Y
authors.lastname: Zhang
authors.forename: Feng-Shuang
authors.initials: FS
authors.lastname: An
mesh_terms: D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase / Q000096:biosynthesis* / Q000235:genetics; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000201:enzymology*; D001057:Apolipoproteins E / Q000172:deficiency / Q000235:genetics; D004790:Enzyme Induction; D005822:Genetic Vectors; D006801:Humans; D007150:Immunohistochemistry; D016086:Lentivirus / Q000235:genetics; D008264:Macrophages / Q000187:drug effects / Q000201:enzymology*; D051379:Mice; D018345:Mice, Knockout; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D047495:PPAR gamma / Q000819:agonists / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis; D044042:Receptors, Formyl Peptide / Q000819:agonists / Q000378:metabolism; D044067:Receptors, Lipoxin / Q000819:agonists / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D000685:Serum Amyloid A Protein / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D013997:Time Factors; D020298:U937 Cells
chemical_list: D001057:Apolipoproteins E; C105101:FPR2 protein, human; D047495:PPAR gamma; D047428:Protein Kinase Inhibitors; D012333:RNA, Messenger; D044042:Receptors, Formyl Peptide; D044067:Receptors, Lipoxin; D011994:Recombinant Proteins; C521404:SAA1 protein, human; C489995:Saa2 protein, mouse; D000685:Serum Amyloid A Protein; D020928:Mitogen-Activated Protein Kinases; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase