Increased IL-1beta in cortex of aged rats is accompanied by downregulation of ERK and PI-3 kinase.
Ageing is accompanied by a myriad of changes, which lead to deficits in synaptic function and recent studies have identified an increase in concentration of the proinflammatory cytokine, interleukin-1beta (IL-1beta), as a factor which significantly contributes to deterioration of cell function. Here, we consider that increased IL-1beta concentration and upregulation of IL-1beta-induced cell signalling cascades may be accompanied by downregulation of survival signals, perhaps as a consequence of decreased neurotrophins-associated signalling. The data indicate that increased IL-1beta concentration was coupled with downregulation of ERK and phosphoinositide-3 kinase (PI-3 kinase) in cortical tissue prepared from aged rats. These changes could not be attributed to decreased concentration of NGF or BDNF but the evidence suggested that they may be a consequence of an age-related change in the anti-inflammatory cytokine, IL-4. Significantly, treatment of aged rats with eicosapentaenoic acid reversed the age-related increases in IL-1beta and IL-1beta-induced signalling and also the age-related changes in IL-4, ERK and PI-3 kinase.
Maher
F O
FO
Department of Physiology, Trinity College Institute of Neuroscience, Trinity College, Dublin 2, Ireland.
Martin
D S D
DS
Lynch
M A
MA
D000375:Aging / Q000378:metabolism*; D000818:Animals; D001426:Bacterial Proteins / Q000378:metabolism; D015153:Blotting, Western / Q000379:methods; D019208:Brain-Derived Neurotrophic Factor / Q000032:analysis; D002070:Butadienes / Q000494:pharmacology; D002352:Carrier Proteins / Q000378:metabolism; D053148:Caspase 3; D020169:Caspases / Q000494:pharmacology; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000378:metabolism*; D002867:Chromones / Q000494:pharmacology; D015536:Down-Regulation; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D007375:Interleukin-1 / Q000378:metabolism* / Q000494:pharmacology; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D009025:Morpholines / Q000494:pharmacology; D020932:Nerve Growth Factor / Q000032:analysis; D009570:Nitriles / Q000494:pharmacology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D020917:Receptor, trkA; D017472:Receptors, Interleukin-1 / Q000378:metabolism
D001426:Bacterial Proteins; D019208:Brain-Derived Neurotrophic Factor; D002070:Butadienes; D002352:Carrier Proteins; D002867:Chromones; D004791:Enzyme Inhibitors; D007375:Interleukin-1; D008565:Membrane Proteins; D009025:Morpholines; D009570:Nitriles; D017472:Receptors, Interleukin-1; C113580:U 0126; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D020932:Nerve Growth Factor; D019869:Phosphatidylinositol 3-Kinases; D020917:Receptor, trkA; D020928:Mitogen-Activated Protein Kinases; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases