The 5‐lipoxygenase inhibitor, zileuton, suppresses prostaglandin biosynthesis by inhibition of arachidonic acid release in macrophages

摘要: BACKGROUND AND PURPOSE Zileuton is the only 5-lipoxygenase (5-LOX) inhibitor marketed as a treatment for asthma, and often utilized selective tool to evaluate role of 5-LOX leukotrienes. The aim this study was investigate effect zileuton on prostaglandin (PG) production in vitro vivo. EXPERIMENTAL APPROACH Peritoneal macrophages activated with lipopolysaccharide (LPS)/interferon γ (LPS/IFNγ), J774 human whole blood stimulated LPS were used models rat carrageenan-induced pleurisy an vivo model. KEY RESULTS suppressed PG biosynthesis by interference arachidonic acid (AA) release macrophages. We found that significantly reduced PGE2 6-keto F1α (PGF1α) levels mouse peritoneal This not related inhibition, because it also observed from knockout mice. Notably, inhibited LPS-stimulated PGF1α pleural pleurisy. Interestingly, failed inhibit activity microsomal synthase1 cyclooxygenase (COX)-2 did affect COX-2 expression. However, decreased AA accompanied inhibition phospholipase A2 translocation cellular membranes. CONCLUSIONS IMPLICATION interfering at level release. Its mechanism action, well its use pharmacological tool, experimental inflammation should be reassessed.