title: Proton pump inhibitors exert anti-inflammatory effects and decrease human microglial and monocytic THP-1 cell neurotoxicity.
abstract: To explore whether proton pump inhibitors (PPIs) possess anti-inflammatory effects on microglia, we investigated the effect of lansoprazole (LPZ) and omeprazole (OPZ) on the toxic action towards SH-SY5Y neuroblastoma cells of supernatants from human microglia and THP-1 cells stimulated by lipopolysaccharide combined with interferon-gamma. In addition, we studied the effect of LPZ and OPZ on the THP-1 cell production of the pro-inflammatory cytokines tumor necrosis factor (TNF)-alpha and interleukin (IL)-6 using enzyme-linked immunosorbent assays. We found that both PPIs had a protective effect on the toxicity of supernatants and that there was a synergism of this effect with S-ibuprofen (IBP), a typical non-steroidal anti-inflammatory drug (NSAID). A similar protective effect of LPZ was observed with supernatants from stimulated human microglia. We also found that both PPIs significantly reduced the TNF-alpha secretion from stimulated THP-1 cells in a concentration dependent manner and that there was a trend towards such reduction of IL-6. These results indicate that PPIs possess anti-inflammatory effects and can decrease human microglial and monocytic neurotoxicity. They suggest that PPIs combined with NSAIDs may be effective in the treatment of a broad spectrum of neurodegenerative diseases associated with activated microglia.
authors.affiliation: Department of Psychiatry, Kinsmen Laboratory of Neurological Research, The University of British Columbia, Vancouver, BC, Canada.
authors.forename: Sadayuki
authors.initials: S
authors.lastname: Hashioka
authors.forename: Andis
authors.initials: A
authors.lastname: Klegeris
authors.forename: Patrick L
authors.initials: PL
authors.lastname: McGeer
mesh_terms: D053799:2-Pyridinylmethylsulfinylbenzimidazoles / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D006801:Humans; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy*; D007371:Interferon-gamma / Q000633:toxicity; D015850:Interleukin-6 / Q000378:metabolism; D064747:Lansoprazole; D017628:Microglia / Q000187:drug effects*; D009000:Monocytes / Q000187:drug effects*; D009447:Neuroblastoma; D009853:Omeprazole / Q000494:pharmacology*; D011134:Polysaccharides / Q000633:toxicity; D054328:Proton Pump Inhibitors / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D015850:Interleukin-6; D011134:Polysaccharides; D054328:Proton Pump Inhibitors; D014409:Tumor Necrosis Factor-alpha; D064747:Lansoprazole; D007371:Interferon-gamma; D009853:Omeprazole