Interleukin-1 receptor antagonist.
The interleukin-1 receptor antagonist (IL-1ra) is unusual in that it is the only known naturally occurring, cytokine receptor antagonist with no apparent agonist function. Over the last 5 years, since the cloning of the IL-1ra cDNA sequence, there has been intensive research on the genetics, regulation, and potential therapeutic value of this protein. The later discovery of a second form of IL-1ra in 1991 has complicated the picture. Whereas the originally described IL-1ra is predominantly glycosylated and secreted (sIL-1ra), the alternative isoform is unglycosylated and intracellular (icIL-1ra). Although the biological roles of the two forms are still open to question, IL-1ra is likely to be of great importance in the pathogenesis of both acute and chronic inflammatory diseases. A large body of evidence for this conclusion has come from animal models of inflammatory disease that respond well to administration of exogenous IL-1ra. A role for recombinant IL-1ra in the management of human disease is still under investigation. The two forms of IL-1ra are encoded by a single gene by alternative usage of two first exons. Expression of sIL-1ra and icIl-1ra is regulated by two promoters. In this review I explore the genetics of the gene encoding IL-1ra (IL-1RN) and the mechanisms of IL-1ra gene activation to produce sIL-1ra and icIL-1ra. Also, possible biological roles for these immunomodulators in health and disease are discussed.
Yamanouchi Research Institute U.K., Littlemore Hospital, Oxford, U.K.
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Lennard
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D003001:Cloning, Molecular; D005786:Gene Expression Regulation; D005796:Genes; D006031:Glycosylation; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use; D007249:Inflammation / Q000503:physiopathology / Q000628:therapy; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000037:antagonists & inhibitors / Q000502:physiology; D008264:Macrophages / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009000:Monocytes / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011487:Protein Conformation; D011499:Protein Processing, Post-Translational; D011817:Rabbits; D017472:Receptors, Interleukin-1 / Q000502:physiology; D012795:Sialoglycoproteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology / Q000627:therapeutic use; D015533:Transcriptional Activation
C507763:IL1RN protein, human; D007155:Immunologic Factors; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D017472:Receptors, Interleukin-1; D012795:Sialoglycoproteins