Recombinant Human IL-1 RII Fc Chimera Protein, CF

IL-1 Receptor II (also IL‑1 R2) is a 60 ‑ 70 kDa member of the interleukin‑1 receptor family of proteins (1 ‑ 4). It serves as a non‑signaling ligand‑binding decoy receptor for IL‑1 beta and IL‑1 alpha (4). IL‑1 binds to a cell surface complex composed of IL‑1 RI and IL‑1 RAcP. Upon activation, this complex recruits MyD88 for downstream signaling (4, 5). The proinflammatory action of IL-1 is antagonized by IL‑1ra which binds to IL‑1 RI but does not initiate signaling. A second natural antagonist is IL‑1 RII, a cell surface receptor that binds both IL‑1 alpha and beta, but not IL‑1ra. IL‑1 RII is found on astrocytes, neutrophils, anterior pituitary acidophils that secrete GH, corneal epithelium, testicular Leydig and Sertoli cells, B cells and monocytes/macrophages (6 ‑ 12). Mature human IL‑1 RII is a 385 amino acid (aa) type I transmembrane glycoprotein that contains a 330 aa extracellular region with three Ig‑like domains (aa 14 ‑ 343), a 26 aa transmembrane segment, and a 29 aa cytoplasmic domain with no signaling motifs (13). There is one soluble 55 ‑ 60 kDa alternative splice form that shows a premature truncation after Gln296 (14). ARTS‑1 mediated cleavage of IL-1 RII generates a 47 kDa isoform, while alpha‑secretase cleavage after Arg338 creates a 50 ‑ 55 kDa isoform that undergoes further processing back to Pro314 (15, 16). Human IL‑1 RII shares 59% aa identity with mouse IL‑1 RII in the extracellular region. Different forms of human IL‑1 RII demonstrate differing binding affinities for IL‑1. IL‑1 RII has a preference for IL‑1 beta over IL‑1 alpha, and binding requires the presence of IL‑1 RAcP. This interaction prevents the association of IL‑1 with IL‑1 RI and also restricts IL‑1 R to a non‑signaling receptor complex (11, 17 ‑ 19). The membrane IL‑1 RII:IL‑1 RAcP complex does not form a functional bond with IL‑1ra, and cannot bind pro‑IL‑1 beta (11, 13, 19, 20). Soluble IL‑1 RII, by contrast, demonstrates a different binding profile. Notably, it will bind pro‑IL‑1 beta rendering it unavailable for activation by extracellular proteases (19, 20). Although it will sequester both IL‑1 beta and IL‑1 alpha, its interaction with soluble IL‑1 RAcP creates a circulating high affinity complex for both IL‑1 beta and IL‑1 alpha, thus potentiating its anti‑inflammatory activity.