An in vitro model of inflammatory neurodegeneration and its neuroprotection.
Inflammation has been implicated in a variety of acute and chronic neurodegenerative diseases in which the inflammatory processes are considered not only to result from neurodegenerative effects, but also to contribute to these effects. To investigate the primary effect of inflammation on neuronal survival, a co-culture system of neuronal cells (differentiated SH SY5Y human neuroblastoma cells or primary cortical/striatal neurons) and monocytic cells (THP-1) in direct cell-cell contact was set up. After 5 days, THP-1 activation by lipopolysaccharide and phorbol 12-myristate 13-acetate resulted in a significant increase of neuronal cell death compared to co-culture without activation. In neuroprotection studies using this model, ascorbic acid and EDTA demonstrated a highly significant reduction in activated THP-1 induced cell death. Glutathione and NBQX, but not the protease inhibitor, PMSF, and catalase, also significantly reduced this inflammatory neurotoxicity. Indomethacin was protective of the primary cultured neurons but not the SH SY5Y cells. This co-culture of neuronal cells and activated THP-1 provides a useful model for the study of inflammatory mechanisms resulting in neuronal cell death.
Messmer
Kirsten
K
University of Sheffield, Department of Biomedical Science, Western Bank, Sheffield S10 2TN, UK. kmess001@umaryland.edu
Reynolds
Gavin P
GP
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D002374:Catalase / Q000494:pharmacology; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects* / Q000502:physiology; D002478:Cells, Cultured; D002614:Chelating Agents / Q000494:pharmacology; D018920:Coculture Techniques; D004660:Encephalitis / Q000188:drug therapy* / Q000378:metabolism* / Q000503:physiopathology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D006801:Humans; D018836:Inflammation Mediators / Q000494:pharmacology; D051379:Mice; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism; D019636:Neurodegenerative Diseases / Q000188:drug therapy* / Q000378:metabolism* / Q000503:physiopathology; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology; D011480:Protease Inhibitors / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D000975:Antioxidants; D002614:Chelating Agents; D018691:Excitatory Amino Acid Antagonists; D018836:Inflammation Mediators; D018696:Neuroprotective Agents; D011480:Protease Inhibitors; D002374:Catalase