Recombinant Mouse IL-36Ra/IL-1F5 Protein

Mouse interleukin-36 receptor antagonist (IL-36Ra; previously IL-1F5; also named FIL-1 delta [delta], IL‑1HY1, IL-1H3, and IL-1L1) is a member of the IL‑1 family of proteins (1-6). IL‑1 family members include IL-1 beta, IL-1 alpha, IL-1ra, IL‑18 and IL‑1F5 through F10 (6, 7). All family members show a 12 beta-strand, beta-trefoil configuration, and are believed to have arisen from a common ancestral gene that underwent multiple duplications (8). The mouse IL‑36Ra/IL‑1F5 gene maps to a region on mouse chromosome 2 that contains all other IL-1 family members (except IL‑18), supporting an evolutionary relationship with the IL-1 family (1, 9). It is particularly close to the gene for IL-1ra and is likely a relatively recent duplication of that gene. IL‑36Ra/IL‑1F5 is synthesized as a 156 amino acid (aa) protein that contains no signal sequence, no prosegment and no potential N-linked glycosylation site(s) (2, 5, 8). Nevertheless, it appears to be secreted as a 17 kDa monomer. In humans, there is an alternate start site that potentially gives rise to an alternate splice form (5). This translated product has a premature stop codon, resulting in a truncated 16 aa peptide. Mouse to human, full length IL‑36Ra/IL‑1F5 has 90% aa identity. Within the family, IL-36Ra/IL-1F5 is 48%, 30%, 35%, 35%, 35%, 37% and 43% aa identical to IL‑1ra, IL‑1 beta, IL‑36 alpha/IL‑1F6, IL‑37/IL‑1F7, IL-36 beta/IL-1F8, IL‑36 gamma/IL‑1F9 and IL‑1F10, respectively. Cells reported to express IL-36Ra/IL-1F5 include monocytes, B cells, dendritic cells/Langerhans cells, keratinocytes, and gastric fundus Parietal and Chief cells (1, 8). The receptor for IL-36Ra/IL-1F5 has not been positively identified. Indirect evidence suggests it is IL‑1 Rrp2 and/or IL-1 RAcP (9). In either case, activity association with receptor binding is unclear. It was initially reported to be an antagonist of  IL-36 gamma activity (4, 7). This would be consistent with its hypothesized relationship to IL‑1ra.