Interleukin-1 receptor antagonist exerts agonist activity in the hippocampus independent of the interleukin-1 type I receptor.
Interleukin-1 receptor antagonist (IL-1ra) selectively and competitively inhibits the actions of IL-1 at its receptors and has not been reported to have agonist activity. This study demonstrates that stimulation of synaptosomes with IL-1ra in vitro, mimicked the effects of IL-1 beta by decreasing glutamate release and increasing JNK phosphorylation. These effects of IL-1ra, but not IL-1 beta, were maintained in IL-1 type I receptor (IL-1RI) defective mice. IL-1 beta blocked these IL-1ra-induced effects suggesting that it may also act independently of IL-1RI in some circumstances. Furthermore, IL-1ra mimicked the inhibitory effect of IL-1 beta on long-term potentiation (LTP) in the hippocampus. These data, taken together with our findings that IL-1ra binds to hippocampal synaptosomes in the absence of IL-1RI, provide evidence that IL-1ra exerts agonist activity in the hippocampus independent of IL-1RI.
Loscher
Christine E
CE
Immune Regulation Research Group, Department of Biochemistry, Trinity College, Dublin 2, Ireland.
Mills
Kingston H G
KH
Lynch
Marina A
MA
D000818:Animals; D005260:Female; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism*; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D051381:Rats; D017208:Rats, Wistar; D017472:Receptors, Interleukin-1 / Q000819:agonists* / Q000037:antagonists & inhibitors* / Q000172:deficiency / Q000235:genetics; D012795:Sialoglycoproteins / Q000378:metabolism / Q000494:pharmacology*
C507764:Il1rn protein, mouse; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D017472:Receptors, Interleukin-1; D012795:Sialoglycoproteins