International Immunology, Vol 9, 1581-1588, Copyright © 1997 by Oxford University Press
NF Spencer, ME Poynter, SY Im and RA Daynes
The pathophysiology of many disease states observed in aged individuals has
been linked to the dysregulated production of several pleiotropic
cytokines. We have demonstrated that NF-kappa B, a major transcriptional
regulator of these aberrantly expressed cytokines, exists in a
constitutively activated state in cells obtained from the major lymphoid
organs of aged animals. Therapeutic treatment with dietary antioxidants or
with agents capable of activating the peroxisome proliferator-activated
receptor (PPAR)-alpha was able to correct the abnormal nuclear NF-kappa B
activity, reduce lipid peroxide levels, and eliminate the dysregulated
expression of cytokines and other genes under NF-kappa B control. These
results suggest that abnormal activation of NF-kappa B in aging contributes
to the dysregulated expression of certain pleiotropic cytokines. Effective
therapeutic regimens for aging and other inflammatory disease states might
benefit from the administration of antioxidants or other agents which
specifically activate PPAR-alpha.
ARTICLES
Constitutive activation of NF-kappa B in an animal model of aging
Department of Pathology, University of Utah, Salt Lake City 84132, USA.
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