The soluble form of IL-1 receptor accessory protein enhances the ability of soluble type II IL-1 receptor to inhibit IL-1 action.
Regulation of the activity of the proinflammatory cytokine IL-1 is complex, involving transcriptional and translational control, precursor processing, a receptor antagonist (IL-1ra), and a decoy receptor. Here we report that the soluble form of the IL-1 receptor accessory protein (AcP) increases the affinity of binding of human IL-1alpha and IL-1beta to the soluble human type II IL-1 receptor by approximately 100-fold, while leaving unaltered the low binding affinity of IL-1ra. Soluble AcP is present in normal human serum at an average concentration greater than 300 ng/ml. These findings suggest that the soluble form of IL-1R AcP contributes to the antagonism of IL-1 action by the type II decoy receptor, adding another layer of complexity to the regulation of IL-1 action.
Smith
Dirk E
DE
Amgen Corporation, 51 University Street, Seattle, WA 98101, USA.
Hanna
Roberta
R
Della Friend
Moore
Heather
H
Chen
Hongbo
H
Farese
Ann M
AM
MacVittie
Thomas J
TJ
Virca
G Duke
GD
Sims
John E
JE
D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D006801:Humans; D007249:Inflammation / Q000276:immunology; D018836:Inflammation Mediators / Q000378:metabolism; D007375:Interleukin-1 / Q000378:metabolism*; D053577:Interleukin-1 Receptor Accessory Protein; D007700:Kinetics; D008253:Macaca mulatta; D008969:Molecular Sequence Data; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D017472:Receptors, Interleukin-1 / Q000378:metabolism*; D053574:Receptors, Interleukin-1 Type II; D011994:Recombinant Proteins / Q000378:metabolism; D012995:Solubility
C507765:IL1RAP protein, human; D018836:Inflammation Mediators; D007375:Interleukin-1; D053577:Interleukin-1 Receptor Accessory Protein; D011506:Proteins; D017472:Receptors, Interleukin-1; D053574:Receptors, Interleukin-1 Type II; D011994:Recombinant Proteins