Staphylococcal exoproducts down-regulate cyclooxygenase 1 and 2 in peritoneal macrophages.

Peritoneal macrophages (PMOs) are important components of the host defense against microbial infection in patients undergoing continuous ambulatory peritoneal dialysis (CAPD). Incubation of human PMOs with cell-free supernatant (BFS), prepared from Staphylococcus aureus, inhibited prostaglandin E2 (PGE2) and thromboxane B2 (TXB2) production. Slot-blot analysis of cyclooxygenase-1 (Cox-1) and Cox-2 demonstrated a decrease in both Cox-1 (29%) and, to a greater extent, Cox-2 (65%) protein expression after BFS stimulation. When competitive polymerase chain reaction (PCR) was used, the peak levels of Cox-1 and Cox-2 messenger ribonucleic acid (mRNA) in unstimulated PMOs were 0.304+/-0.13 pmol/L and 9.61+/-2.84 pmol/L (mean+/-SEM, n = 3), respectively. After exposure of samples to BFS for 30 minutes, the level of Cox-2 mRNA was reduced to 0.59+/-0.449 pmol/L (16-fold reduction, p < 0.05), and the level of Cox-1 mRNA was reduced to 0.02+/-0.002 pmol/L (15-fold reduction, p < 0.05). In contrast, these same PMOs showed an increased expression of IL-6 mRNA and increased secretion of IL-6 protein. These results indicate that prostaglandin production in PMOs is regulated by alterations in both immunoreactive Cox-1 and Cox-2. The down-regulation of Cox metabolism in these cells is primarily related to the delayed and depressed increase in the Cox-2 gene product.