Influence of neurons on lipopolysaccharide-stimulated production of nitric oxide and tumor necrosis factor-alpha by cultured glia

Brain Res. 2000 Jan 24;853(2):236-44. doi: 10.1016/s0006-8993(99)02255-6.

Abstract

Cerebral inflammation often originates in a region where neuronal death occurs and thereafter slowly spreads outward. This study aimed to elucidate the roles of neurons in modulating the production of inflammatory factors stimulated by the bacterial endotoxin lipopolysaccharide (LPS). Culturing neurons with mixed glia reduced nitrite and tumor necrosis factor-alpha (TNF-alpha) production compared to cultures with only mixed glia, and shifted the dose-response curve to the right. The decreased nitrite and TNF-alpha production were not due to the cytotoxicity of LPS. Immunocytochemical analysis of glia-neuron co-cultures revealed the morphological changes in the activated microglia. Culturing PC12 cells with rat mixed-glia also reduced nitrite production. The influence of neurons on glial inflammation was partly due to the cell-cell contacts between neurons and glia via neural cell adhesion molecules (NCAM) because NCAM significantly reduced LPS-stimulated nitrite production. These results demonstrate that neurons reduce the production of inflammatory factors by glia. Since cerebral inflammation is important in many neurological disorders, this study might provide insight about the role of glia-neuron interactions in inflammatory responses in the brain.

MeSH terms

  • Animals
  • Animals, Newborn
  • Cell Communication / drug effects
  • Cell Size / drug effects
  • Cells, Cultured
  • Coculture Techniques
  • Dose-Response Relationship, Drug
  • Down-Regulation
  • Inflammation / chemically induced
  • Inflammation / metabolism
  • L-Lactate Dehydrogenase / metabolism
  • Lipopolysaccharides / pharmacology*
  • Mice
  • Neural Cell Adhesion Molecules / metabolism
  • Neural Cell Adhesion Molecules / pharmacology
  • Neuroglia / cytology
  • Neuroglia / drug effects*
  • Neuroglia / enzymology
  • Neurons / cytology
  • Neurons / metabolism*
  • Nitric Oxide / biosynthesis*
  • Nitric Oxide Synthase / metabolism
  • Nitric Oxide Synthase Type II
  • PC12 Cells
  • Rats
  • Rats, Inbred F344
  • Tumor Necrosis Factor-alpha / biosynthesis*

Substances

  • Lipopolysaccharides
  • Neural Cell Adhesion Molecules
  • Tumor Necrosis Factor-alpha
  • Nitric Oxide
  • L-Lactate Dehydrogenase
  • Nitric Oxide Synthase
  • Nitric Oxide Synthase Type II
  • Nos2 protein, mouse
  • Nos2 protein, rat