A tissue specific IL-1 receptor antagonist homolog from the IL-1 cluster lacks IL-1, IL-1ra, IL-18 and IL-18 antagonist activities.
Interleukin (IL)-1-like protein 1 (IL-1L1) is a 155-amino acid protein that shares 27% identity with IL-1beta and 47% with IL-1 receptor antagonist (IL-1ra). A 2.7-kb IL-1L1 mRNA was cloned from human placenta and is detectable in the trophoblastic cell line JEG-3, in macrophages and in endotoxin-stimulated monocytes. Expression of IL-1L1 is much less abundant and less widespread than IL-1ra. We have determined the human and mouse IL-1L1 cDNA sequences and the complete sequence of the human gene, IL1L1. IL1L1 consists of four coding exons, has two alternative non-coding first exons, lies between IL1B and IL1RN, is orientated in the same direction as IL1RN and is separated from it by approximately 53 kb. The predicted IL-1L1 protein lacks both signal sequence and glycosylation signals. A 17-kDa protein was recovered by immunoprecipitation with IL-1L1-specific antibodies from JEG-3. IL-1L1 did not stimulate IL-6 production from primary human fibroblasts or human umbilical vein endothelial cells nor did it block the IL-1alpha or IL-1beta-dependent activation of IL-6 expression. We conclude, contrary to a recent suggestion made by others, that IL-1L1 is not a functional IL-1ra. IL-1L1 also had no detectable agonistic or antagonistic effect on IFN-gamma production in response to IL-18 in KG-1 cells.
Barton
J L
JL
Division of Molecular and Genetic Medicine, University of Sheffield, Sheffield, GB.
Herbst
R
R
Bosisio
D
D
Higgins
L
L
Nicklin
M J
MJ
D000595:Amino Acid Sequence; D000818:Animals; D018076:DNA, Complementary / Q000235:genetics / Q000276:immunology; D005786:Gene Expression Regulation / Q000276:immunology*; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000235:genetics / Q000276:immunology*; D020382:Interleukin-18 / Q000235:genetics / Q000276:immunology*; D053727:Interleukin-18 Receptor alpha Subunit; D051379:Mice; D008969:Molecular Sequence Data; D005810:Multigene Family / Q000276:immunology*; D009928:Organ Specificity; D018123:Receptors, Interleukin / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology*; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology*; D053724:Receptors, Interleukin-18; D016415:Sequence Alignment; D012795:Sialoglycoproteins / Q000235:genetics / Q000276:immunology*; D014158:Transcription, Genetic
D018076:DNA, Complementary; C508572:IL18R1 protein, human; C507763:IL1RN protein, human; C508573:Il18r1 protein, mouse; C507764:Il1rn protein, mouse; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D020382:Interleukin-18; D053727:Interleukin-18 Receptor alpha Subunit; D018123:Receptors, Interleukin; D017472:Receptors, Interleukin-1; D053724:Receptors, Interleukin-18; D012795:Sialoglycoproteins