beta-Amyloid induction of gelatinase B secretion in cultured microglia: inhibition by dexamethasone and indomethacin.

Since administration of anti-inflammatory drugs has been reported to possibly slow the progression of Alzheimer's disease, an effort was made to define effector functions induced by beta-amyloid (A beta) which may be inhibited by these drugs. Rat microglia in culture were treated with various A beta fragments and gelatinase (GLase) activity was determined using gelatin-substrate zymography; the ability of indomethacin (INDO) and dexamethasone (DEX) to inhibit A beta-stimulated GLase, specifically matrix metalloproteinase-9 (MMP-9), activity was also evaluated. A beta (1-38) and A beta (1-40) were effective in stimulating MMP-9 activity in a dose-dependent fashion. Co-treatment with INDO (50 microM) or DEX (100 nM) resulted in a 54% and 66% inhibition, respectively, of A beta (1-40)-stimulated MMP-9 production in microglia.