Analysis of interleukin-1 beta-induced cell signaling activation in rat hippocampus following exposure to gamma irradiation. Protective effect of eicosapentaenoic acid.
Among the many reported effects of irradiation in cells is activation of the stress-activated protein kinase, c-Jun N-terminal kinase (JNK), which has been shown to result in apoptotic cell death. The trigger that leads to JNK activation has not been identified, although, in rat hippocampus at least, irradiation-induced apoptosis has been coupled with increased accumulation of reactive oxygen species (ROS). Significantly, irradiation-induced changes in hippocampus are abrogated by treatment of rats with the polyunsaturated fatty acid, eicosapentaenoic acid (EPA). A close coupling between ROS accumulation and concentration of the pro-inflammatory cytokine, interleukin-1 beta (IL-1 beta) in hippocampus has been reported, and the evidence suggests that IL-1 beta may be responsible for the enhanced ROS production. Here we set out to assess the possibility that whole body gamma-irradiation increases IL-1 beta concentration in hippocampus and to investigate the consequences of such a change. We present evidence that reveals that the irradiation-induced increase in IL-1 beta concentration in hippocampus is accompanied by increased expression of IL-1 type I receptor and IL-1 accessory protein and increased activation of IL-1 receptor-activated kinase. These changes, which were coupled with increased activation of JNK and evidence of apoptotic cell death, were absent in hippocampus of rats that received EPA treatment. Significantly, EPA treatment enhanced hippocampal IL-10 concentration that was inversely correlated with IL-1 beta concentration. The data are consistent with the idea that EPA exerts anti-inflammatory and neuroprotective effects in the central nervous system.
Lynch
Aileen M
AM
Department of Physiology, Trinity College Institute of Neuroscience, Trinity College, Dublin 2, Ireland. amlynch@tcd.ie
Moore
Michelle
M
Craig
Sarah
S
Lonergan
Peter E
PE
Martin
Darren S
DS
Lynch
Marina A
MA
D000818:Animals; D017209:Apoptosis; D015118:Eicosapentaenoic Acid; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology; D005720:Gamma Rays; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism*; D007375:Interleukin-1 / Q000528:radiation effects*; D016753:Interleukin-10 / Q000032:analysis; D048031:JNK Mitogen-Activated Protein Kinases; D008297:Male; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D020011:Protective Agents / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000528:radiation effects*; D015854:Up-Regulation; D014916:Whole-Body Irradiation
D005231:Fatty Acids, Unsaturated; D007375:Interleukin-1; D020011:Protective Agents; D016753:Interleukin-10; D015118:Eicosapentaenoic Acid; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases