Sodium salicylate and 17 beta-estradiol attenuate nuclear transcription factor NF-kappa B translocation in cultured rat astroglial cultures followingexposure to amyloid A beta(1-40) and lipopolysaccharides

In recent years inflammatory mechanisms have become increasingly appreciate d as important steps in the Alzheimer's pathogenic pathway. There is accumu lating 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 add ition, clinical studies using nonsteroidal antiinflammatory drugs have foun d a reduced risk for Alzheimer's disease with their use. Here we show that the neurotoxic A beta, a major plaque component, and lipopolysaccharides (L PS), an immune reaction-triggering portion of bacterial membranes, are both potent activators of the nuclear transcription factor NF-kappa B in primar y rat astroglial cells. The activation was found to be concentration- and t ime-dependent and could be attenuated in the presence of NF-kappa B decoy n ucleotides. The pretreatment by either 17 beta-estradiol (1-10 mu g) or sod ium salicylate (3-30 mM) reduced the A beta (LPS)-induced activation of NF- kappa B by 48 (50%) and 60% (50%) of activated levels, respectively. In add ition, 17 beta-estradiol (10 mu M) and sodium salicylate (10 mM) were able to attenuate the increase in interleukin-1 beta levels following exposure t o 25 mu M A beta, Our data suggest that the aberrant gene expression is at least in part due to A beta-induced activation of NF-kappa B, a potent imme diate-early transcriptional regulator of numerous proinflammatory genes; th is event takes place in astroglial cells. The results of our experiments pr ovide a further understanding of the effects of estrogen and aspirin on ast roglial cells exposed to A beta and LPS.