Effects of TNF-α and IL-1β on the Expression of Pregnancy-Associated Plasma Protein-A in Endothelial Cells and Its Mechanism

Aim To investigate the effects of tumor necrosis factor-α(TNF-α)and interleukin-1β(IL-1β)on pregnancy-associated plasma protein-A(PAPP-A)expression in endothelial cells and analyse its mechanism.Methods The rat aortic endothelial cells were obtained from thoracic aortas and cultured by tissue explant method.Passage 3～4 cells were used in the experiment.Rortic endothelial cells were coincubated with different concentrations of TNF-α(10,20,40,60 and 100 μg/L)and IL-1β(1,5,10,20 and 50 μg/L)for 24 h or coincubated with 60 μg/L TNF-α,20 μg/L IL-1β for different periods(2,4,8,16,24 and 48 h).BAY11-7082(20 μmol/L)was pretreated for 60 min before rortic endothelial cells were coincubated with 60 μg/L TNF-α,20 μg/L IL-1β for 48 h.LDH activity in supernatant was detected.PAPP-A mRNA and protein expression were detected by RT-PCR or ELISA.Results After the intervention of TNF-α or IL-1β for 24 h,the levels of PAPP-A expression increased with the concentration raise(P0.05);Cytokines stimulated PAPP-A expression in the two groups(P0.05);BAY11-7082 inhibited PAPP-A expression stimulated by TNF-α and IL-1β.Conclusions TNF-α and IL-1β may stimulate the expression of PAPP-A,nuclear factor-κB(NF-κB)activation may be the primary mediator of cytokines stimulated PAPP-A expression.