Sodium salicylate and 17beta-estradiol attenuate nuclear transcription factor NF-kappaB translocation in cultured rat astroglial cultures following exposure to amyloid A beta(1-40) and lipopolysaccharides - PubMed (original) (raw)
Sodium salicylate and 17beta-estradiol attenuate nuclear transcription factor NF-kappaB translocation in cultured rat astroglial cultures following exposure to amyloid A beta(1-40) and lipopolysaccharides
R C Dodel et al. J Neurochem. 1999 Oct.
Free article
Abstract
In recent years inflammatory mechanisms have become increasingly appreciated as important steps in the Alzheimer's pathogenic pathway. There is accumulating evidence that amyloid beta-peptide (A beta), 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 A beta, 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-kappaB in primary rat astroglial cells. The activation was found to be concentration- and time-dependent and could be attenuated in the presence of NF-kappaB decoy nucleotides. The pretreatment by either 17beta-estradiol (1-10 microg) or sodium salicylate (3-30 mM) reduced the A beta (LPS)-induced activation of NF-kappaB by 48 (50%) and 60% (50%) of activated levels, respectively. In addition, 17beta-estradiol (10 microM) and sodium salicylate (10 mM) were able to attenuate the increase in interleukin-1beta levels following exposure to 25 microM A beta. Our data suggest that the aberrant gene expression is at least in part due to A beta-induced activation of NF-kappaB, 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 A beta and LPS.
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