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BACKGROUND
Inheritance of the three different alleles of the human apolipoprotein (apo) E gene (APOE) are associated with varying risk or clinical outcome from a variety of neurologic diseases. ApoE isoform-specific modulation of several pathogenic processes, in addition to amyloid beta metabolism in Alzheimer's disease, have been proposed: one of these is innate immune response by glia. Previously we have shown that primary microglia cultures from targeted replacement (TR) APOE mice have apoE isoform-dependent innate immune activation and paracrine damage to neurons that is greatest with TR by the epsilon4 allele (TR APOE4) and that derives from p38 mitogen-activated protein kinase (p38MAPK) activity.METHODS
Primary cultures of TR APOE2, TR APOE3 and TR APOE4 astrocytes were stimulated with lipopolysaccharide (LPS). ApoE secretion, cytokine production, and nuclear factor-kappa B (NF-kappaB) subunit activity were measured and compared.RESULTS
Here we showed that activation of primary astrocytes from TR APOE mice with LPS led to TR APOE-dependent differences in cytokine secretion that were greatest in TR APOE2 and that were associated with differences in NF-kappaB subunit activity.CONCLUSIONS
Our results suggest that LPS activation of innate immune response in TR APOE glia results in opposing outcomes from microglia and astrocytes as a result of TR APOE-dependent activation of p38MAPK or NF-kappaB signaling in these two cell types.
p38MAPK → APOE: " Our results suggest that LPS activation of innate immune response in TR APOE glia results in opposing outcomes from microglia and astrocytes as a result of TR APOE dependent activation of p38MAPK or NF-kappaB signaling in these two cell types "
LPS → p38MAPK: " Our results suggest that LPS activation of innate immune response in TR APOE glia results in opposing outcomes from microglia and astrocytes as a result of TR APOE dependent activation of p38MAPK or NF-kappaB signaling in these two cell types "
LPS → p38MAPK: " Our results suggest that LPS activation of innate immune response in TR APOE glia results in opposing outcomes from microglia and astrocytes as a result of TR APOE dependent activation of p38MAPK or NF-kappaB signaling in these two cell types "
LPS → APOE: " Our results suggest that LPS activation of innate immune response in TR APOE glia results in opposing outcomes from microglia and astrocytes as a result of TR APOE dependent activation of p38MAPK or NF-kappaB signaling in these two cell types "
LPS → NF-kappaB: " Our results suggest that LPS activation of innate immune response in TR APOE glia results in opposing outcomes from microglia and astrocytes as a result of TR APOE dependent activation of p38MAPK or NF-kappaB signaling in these two cell types "
NF-kappaB → APOE: " Our results suggest that LPS activation of innate immune response in TR APOE glia results in opposing outcomes from microglia and astrocytes as a result of TR APOE dependent activation of p38MAPK or NF-kappaB signaling in these two cell types "