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

Area of Science:

• Immunology
• Cell Biology
• Microbiology

Background:

• Peritoneal macrophages (PMOs) are crucial for host defense against infections in continuous ambulatory peritoneal dialysis (CAPD) patients.
• Microbial infections can compromise the effectiveness of the peritoneal membrane in CAPD.
• Prostaglandins play a role in the inflammatory response of PMOs.

Purpose of the Study:

• To investigate the effect of Staphylococcus aureus supernatant on prostaglandin production in human PMOs.
• To determine the impact on cyclooxygenase (Cox) enzyme expression and activity.
• To understand the implications for host defense in CAPD.

Main Methods:

• Human PMOs were incubated with cell-free supernatant (BFS) from Staphylococcus aureus.
• Prostaglandin E2 (PGE2) and Thromboxane B2 (TXB2) production were measured.
• Slot-blot analysis was used to assess Cox-1 and Cox-2 protein expression.
• Competitive polymerase chain reaction (PCR) quantified Cox-1 and Cox-2 mRNA levels.
• Interleukin-6 (IL-6) mRNA and protein levels were analyzed.

Main Results:

• BFS significantly inhibited PGE2 and TXB2 production in PMOs.
• Cox-1 protein expression decreased by 29%, and Cox-2 by 65%.
• Both Cox-1 and Cox-2 mRNA levels were significantly reduced (15- and 16-fold, respectively) after BFS exposure.
• IL-6 mRNA and protein expression were increased in response to BFS.
• Down-regulation of Cox metabolism, primarily Cox-2, was observed.

Conclusions:

• Prostaglandin production in PMOs is regulated by alterations in Cox-1 and Cox-2.
• Staphylococcus aureus supernatant down-regulates Cox metabolism in PMOs, mainly via Cox-2.
• These findings suggest a mechanism by which microbial infections may impair host defense in CAPD patients.