title: CRP and TNF-α  induce PAPP-A expression in human peripheral blood mononuclear cells.
abstract: OBJECTIVE
  The effects of C-reactive protein (CRP) and tumor necrosis factor-α (TNF-α) on pregnancy-associated plasma protein-A (PAPP-A) expression in human peripheral blood mononuclear cells (PBMCs) require further investigation.
  
  
  METHODS
  The PAPP-A levels in culture supernatants, PAPP-A mRNA expression, and cellular PAPP-A expression were measured in human PBMCs isolated from fresh blood donations provided by 6 healthy volunteers (4 donations per volunteer). Analyses were conducted by ultrasensitive ELISA, western blotting, and RT-PCR following stimulation with CRP or TNF-α cytokines.
  
  
  RESULTS
  PAPP-A mRNA and protein levels after CRP stimulation peaked at 24 hours, whereas peak PAPP-A mRNA and protein levels were achieved after TNF-α stimulation at only 2 and 8 hours, respectively. These findings indicate the dose-dependent effect of CRP and TNF-α stimulation. Actinomycin D treatment completely prevented CRP and TNF-α induction of PAPP-A mRNA and protein expression. Additionally, nuclear factor- (NF-) κB inhibitor (BAY11-7082) potently inhibited both CRP and TNF-α stimulated PAPP-A mRNA and protein expression.
  
  
  CONCLUSIONS
  Human PBMCs are capable of expressing PAPP-A in vitro, expression that may be regulated by CRP and TNF-α through the NF-κB pathway. This mechanism may play a significant role in the observed increase of serum PAPP-A levels in acute coronary syndrome (ACS).
authors.affiliation: Department of Cardiology, Beijing Friendship Hospital Affiliated to Capital Medical University, Beijing 100050, China.
authors.forename: Weiping
authors.initials: W
authors.lastname: Li
authors.forename: Hongwei
authors.initials: H
authors.lastname: Li
authors.forename: Fusheng
authors.initials: F
authors.lastname: Gu
mesh_terms: D002097:C-Reactive Protein / Q000494:pharmacology*; D002478:Cells, Cultured; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000378:metabolism*; D011266:Pregnancy-Associated Plasma Protein-A / Q000235:genetics / Q000378:metabolism*; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
chemical_list: D014409:Tumor Necrosis Factor-alpha; D002097:C-Reactive Protein; D011266:Pregnancy-Associated Plasma Protein-A