Abstract
The interleukin-1 (IL-1) family comprises IL-1α and IL-1β and an endogenous IL-1 receptor antagonist (IL-1ra).1 IL-1 has diverse actions in the brain and has been implicated in both acute and chronic neurodegeneration.1,2 However, neither IL-1α nor IL-1β are neurotoxic per se in vivo, so other IL-1 related ligands may be important in neurodegeneration. The cytokine interleukin-18 (also called interferon gamma inducing factor, IGIF) was first isolated from the liver of mice during toxic shock.3 It was later proposed as a member of the IL-1 family, based on protein sequence homology with IL-1β and IL-1ra, and has tentatively been called IL-1γ.4 We cloned IL-18 from adult rat brain and demonstrated, by RT-PCR, that it is expressed constitutively in cerebellum, hippocampus, hypothalamus, cortex and striatum. Rat brain IL-18 shows close homology to mouse3 and human IL-18,5 and to the recently published sequence from the rat adrenal gland.6 Mouse pro-IL-18 and pro-IL-1β are processed by caspase-1.7,8 We demonstrate that caspase-1 also cleaves rat IL-18 in vitro and that the caspase inhibitor, zVAD-DCB inhibits this cleavage.
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Culhane, A., Hall, M., Rothwell, N. et al. Cloning of rat brain interleukin-18 cDNA. Mol Psychiatry 3, 362–366 (1998). https://doi.org/10.1038/sj.mp.4000389
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DOI: https://doi.org/10.1038/sj.mp.4000389
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