In recent years inflammatory mechanisms have become increasingly appreciated as important steps in the Alzheimer's pathogenic pathway. There is accumulating evidence that amyloid β-peptide (Aβ), the peptide product of the cleavage of amyloid precursor protein, may promote or exacerbate local inflammation by stimulating glial cells to release immune mediators. In addition, clinical studies using nonsteroidal antiinflammatory drugs have found a reduced risk for Alzheimer's disease with their use. Here we show that the neurotoxic Aβ, a major plaque component, and lipopolysaccharides (LPS), an immune reaction-triggering portion of bacterial membranes, are both potent activators of the nuclear transcription factor NF-κB in primary rat astroglial cells. The activation was found to be concentration- and time- dependent and could be attenuated an the presence of NF-κB decoy nucleotides. The pretreatment by either 17β-estradiol (1-10 μg) or sodium salicylate (3-30 mM) reduced the Aβ (LPS)-induced activation of NF-κB by 48 (50%) and 60% (50%) of activated levels, respectively. In addition, 17β- estradiol (10 μM) and sodium salicylate (10 mM) were able to attenuate the increase in interleukin-1β levels following exposure to 25 μM Aβ. Our data suggest that the aberrant gene expression is at least in part due to Aβ- induced activation of NF-κB, a potent immediate-early transcriptional regulator of numerous proinflammatory genes, this event takes place in astroglial cells. The results of our experiments provide a further understanding of the effects of estrogen and aspirin on astroglial cells exposed to Aβ and LPS.
|Number of pages||8|
|Journal||Journal of Neurochemistry|
|State||Published - Jan 1 1999|
- Alzheimer's disease
- Glial activation
- Nuclear transcription factor NF- κB
- β-Amyloid protein