Effect of inflammatory and antiinflammatory stimuli on acyloxyacyl hydrolase gene expression and enzymatic activity in murine macrophages

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Abstract
Acyloxyacyl hydrolase (AOAH) is an enzyme found in macrophages and neutrophils that specifically cleaves the acyloxyacyl moieties of lipopolysaccharide (LPS), thus rendering it non-toxic for human cells. In the present study, we demonstrate that LPS augments AOAH mRNA expression (10-20-fold) in murine macrophages. Following LPS treatment (100 ng/m]), AOAH mRNA was induced by 2 h, peaked at 6 h, and was sustained over 72 h. Optimal induction of AOAH mRNA was observed with as little as 0.1 ng/ml LPS. LPS also induced a concomitant increase in AOAH enzymatic activity in cytosolic extracts from murine macrophages and the ability of macrophages to deacylate LPS was not diminished in endotoxin-tolerized macrophages. LPS-stimulated AOAH mRNA expression was cycloheximide sensitive, indicating that de novo protein synthesis is required for AOAH mRNA production. Moreover, AOAH mRNA expression was also induced by IFN-γ. LPS-stimulated mRNA expression was not suppressed by either dexamethasone or IL-10. Finally, intraperitoneal challenge of mice with 25 μg of LPS resulted in increases in AOAH mRNA in both the lung (∼3-fold) and in the liver (∼6-fold). A possible role for LPS-inducible AOAH in the elimination of LPS is discussed.