EFFECT OF INFLAMMATORY AND ANTIINFLAMMATORY STIMULI ON ACYLOXYACYL HYDROLASE GENE-EXPRESSION AND ENZYMATIC-ACTIVITY IN MURINE MACROPHAGES

Acyloxyacyl hydrolase (AOAH) is an enzyme found in macrophages and neu trophils that specifically cleaves the acyloxyacyl moieties of lipopol ysaccharide (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/ml ), 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 enzymati c activity in cytosolic extracts from murine macrophages and the abili ty of macrophages to deacylate LPS was not diminished in endotoxin-tol erized macrophages. LPS-stimulated AOAH mRNA expression was cyclohexim ide sensitive, indicating that de novo protein synthesis is required f or AOAH mRNA production. Moreover, AOAH mRNA expression was also induc ed by IFN-gamma. LPS-stimulated mRNA expression was not suppressed by either dexamethasone or IL-10. Finally, intraperitoneal challenge of m ice with 25 mu g of LPS resulted in increases in AOAH mRNA in both the lung (similar to 3-fold) and in the liver (similar to 6-fold). A poss ible role for LPS-inducible AOAH in the elimination of LPS is discusse d.