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  • Title: Proton pump inhibitors exert anti-inflammatory effects and decrease human microglial and monocytic THP-1 cell neurotoxicity.
    Author: Hashioka S, Klegeris A, McGeer PL.
    Journal: Exp Neurol; 2009 May; 217(1):177-83. PubMed ID: 19232345.
    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.
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