Pro-Inflammatory Cytokines and Anti-Inflammatory Drugs Modulate Glial Expression of Apolipoprotein E Protein
Pp. 187-204 (18)
Judes Poirier, Rosanne Aleong and Dorothée Domenger
Alzheimer’s disease (AD) is a neurological disorder characterized by plaques
deposition, neurofibrillary tangle formation and an elevated inflammation. Specifically,
increased expression of interleukin (IL)-1β and tumour necrosis factor (TNF)-α have been
observed in AD cerebrospinal fluid and temporal brain tissue. Conversely, epidemiological
studies have shown that use of non-steroidal anti-inflammatory drugs (NSAIDs) by the
elderly is often associated with a decreased relative risk and a delayed onset of AD. IL-1β
and TNF-α genes were shown to carry genetic polymorphisms that increase the risk of
developing common AD. Studies have also established the apolipoprotein E (apoE) gene to
be a risk factor for AD, with ε4 carriers having been found to show lower levels of brain
apoE protein. In the present study, treatment with IL-1β induced a significant increase in
extracellular apoE protein in primary rat mixed glial cells but not in astrocyte cultures.
Similarly, treatment of primary rat mixed glial cell cultures with the common NSAIDs,
indomethacin and aspirin, induced significant increases in extracellular apoE protein levels.
In contrast, treatment of primary rat astrocyte and mixed glial cell cultures with TNF-α
significantly reduced extracellular apoE protein levels. These results are consistent with the
notion that apoE is an actor of inflammation modulation since its release is regulated by
pro-inflammatory cytokines and dampened by NSAIDs. This further supports the idea that
elevated cytokine expression in AD directly modulates inflammation and indirectly apoEmediated
Alzheimer’s disease, apolipoprotein E, cell culture, interleukin-1β,
non-steroidal anti-inflammatory drugs, tumor necrosis factor-cytokines, lipid,
cholesterols, indomethacin, gene expression, mRNA.
Molecular Neurobiology Unit, 6875 La Salle Blvd., Verdun, Quebec, H4H 1R3, Canada.