Suppression of A beta-induced monocyte neurotoxicity by antiinflammatory compounds.
Previous work from this laboratory has demonstrated that prior exposure of peripheral blood monocytes (PBM) to aggregated beta-amyloid peptide (A beta), the major protein comprising the amyloid plaques characteristically present in the brain of Alzheimer disease (AD)-afflicted individuals, activates these cells to a neurotoxic state when co-cultured with brain tissue. In this report we extend these findings to further show that such A beta-induced PBM neurotoxicity can be inhibited by three differentially-acting antiinflammatory drugs, indomethacin, dexamethasone, and colchicine, which are typically used clinically to treat peripheral inflammatory disease. In addition, evidence is presented that these toxic effects are initiated, in large part, by soluble factors released from A beta-stimulated PBM. Our results suggest a rationale for antiinflammatory therapy in the treatment of AD.
Dzenko
K A
KA
Department of Pharmacology, University of Connecticut Health Center, Farmington 06030, USA.
Weltzien
R B
RB
Pachter
J S
JS
D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002540:Cerebral Cortex / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D018920:Coculture Techniques; D003078:Colchicine / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007213:Indomethacin / Q000494:pharmacology; D009000:Monocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D009498:Neurotoxins / Q000276:immunology* / Q000378:metabolism; D009924:Organ Culture Techniques; D051381:Rats; D011919:Rats, Inbred Strains; D012995:Solubility
D016229:Amyloid beta-Peptides; D000893:Anti-Inflammatory Agents; D007166:Immunosuppressive Agents; D009498:Neurotoxins; D003907:Dexamethasone; D003078:Colchicine; D007213:Indomethacin