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.
Gottschall
P E
PE
University of South Florida College of Medicine, Department of Pharmacology and Therapeutics, Tampa 33612-4799, USA.
D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D017364:Collagenases / Q000096:biosynthesis*; D017077:Culture Media, Conditioned; D003720:Densitometry; D003907:Dexamethasone / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004790:Enzyme Induction / Q000187:drug effects; D007213:Indomethacin / Q000494:pharmacology*; D020780:Matrix Metalloproteinase 9; D017628:Microglia / Q000187:drug effects / Q000201:enzymology*; D051381:Rats
D016229:Amyloid beta-Peptides; D000893:Anti-Inflammatory Agents; D000894:Anti-Inflammatory Agents, Non-Steroidal; D017077:Culture Media, Conditioned; D003907:Dexamethasone; D017364:Collagenases; D020780:Matrix Metalloproteinase 9; D007213:Indomethacin