CRP and TNF-α Induce PAPP-A Expression in Human Peripheral Blood Mononuclear Cells

Abstract EN

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).