Bupivacaine inhibits COX-2 expression;PGE2 and
cytokine production in endotoxin-activated macrophages
蔡佩珊
Huang YHTsai PS;Huang CJ 摘要
Abstract
Background: Upregulation of cyclooxygenase-2 (COX-2) and resultant prostaglandin E2 (PGE2) overproduction has been shown to play a crucial role in initiating a systemic
inflammatory response during sepsis. Sepsis also induces robust production of pro-inflammatory cytokines tumor necrosis factor-α (TNF-α ), interleukin-1β (IL-1β ), and IL-6 as well as anti-inflammatory cytokine IL-10. We sought to elucidate the effects of
bupivacaine on COX-2 expression and production of PGE2 and cytokines using an endotoxin-activated murine macrophages model.
Methods: Confluent murine macrophages (RAW264.7 cells) were treated with lipopolysaccharide (LPS, 100 ng/ml) or LPS plus bupivacaine (1, 10, or 100 μ M). Bupivacaine was added immediately after LPS. After reacting for 18 h, cell cultures were
harvested for subsequent analysis.
Results: LPS significantly upregulated COX-2 transcription and PGE2 production in macrophages. LPS also significantly increased the production of TNF-α , IL-1β , IL-6 and
IL-10 in macrophages. Bupivacaine significantly inhibited the effects of LPS on COX-2 transcription and PGE2 production in a dose-dependent manner. In a dose-dependent manner, bupivacaine also significantly inhibited the effects of LPS on the production of
TNF-α , IL-1β , and IL-6. However, bupivacaine exerted no significant effects on LPS-induced IL-10 production.
Conclusion: Bupivacaine significantly inhibited COX-2 expression, PGE2 and cytokine production in endotoxin-activated macrophages.
