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Production in Rat Macrophages1
*
Institute of Pharmacological Sciences, University of Milan, Milan, Italy;
Department of Neurosciences, University of Rome Tor Vergata, Rome, Italy; and
Institute of Pharmacology, University of Pavia, Pavia, Italy
The ability of macrophages to secrete cytokines is important in
host responses to infections inflammatory stimuli, both of which are
altered with aging. In this study, age-associated changes in the
release of TNF-
from LPS-stimulated rat alveolar macrophages were
determined and correlated with a decrease in the level of RACK1, the
anchoring protein involved in protein kinase C translocation and
activation. Macrophages from aged rats produced 
50% less TNF-
than those from young rats. This effect was observed independently from
the concentration of LPS used and the time considered. The decrease
observed was associated with a defective PKC translocation, due to a
reduction in the expression of RACK1, whereas no differences were
detected in the expression of LPS receptor (CD14) or total PKC isoforms
( and ßII) in old and young rats. Use of RACK1
antisense oligonucleotide reduced the ability of young macrophages to
respond to LPS, further supporting the idea that a deficit in RACK1
contributes to the functional impairment in aged macrophages and that
age-induced macrophage immunodeficiencies are associated with
alteration in signal transduction pathways.
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