Recombinant Human IL-36 beta/IL-1F8 Protein

Human interleukin‑36 beta [IL‑36 beta; previously IL‑1F8 and also named FIL‑1 eta (eta) and IL‑1H2] is a member of the IL‑1 family of proteins (1 ‑ 3, 6). IL‑1 family members include IL‑1 beta, IL‑1 alpha, IL‑1ra, IL‑18, IL‑36Ra/IL‑1F5, IL‑36 alpha/IL‑1F6, IL‑37/IL‑1F7, IL‑36 gamma/IL‑1F9 and IL‑1F10 (4, 6). All family members show a 12 beta‑stranded beta‑trefoil configuration, and are believed to have arisen from a common ancestral gene that has undergone multiple duplications (4). Two alternatively spliced transcript variants encode distinct (164 or 157 residues) protein isoforms that differ in their C‑terminal 70 amino acid (aa) residues have been reported (3). IL‑36 beta/IL‑1F8 isoform 2 is synthesized as a 157 aa protein that contains no signal sequence and no prosegment (1 ‑ 2). Unlike IL‑36 beta/IL‑1F8 isoform 1 which lacks potential N‑linked glycosylation sites, isoform 2 contains one potential N‑linked glycosylation site in its unique C‑terminus. IL‑36 beta/IL‑1F8 is reported to be actively secreted (1). Human IL‑36 beta/IL‑1F8 isoform 2 shares 61% aa identity with mouse IL‑1 ra, a 183 aa form of IL‑36 beta/IL‑1F8. Within the IL‑1 family, IL‑36 beta/IL‑1F8 shares 30%, 32%, 37%, 46%, 34%, 45% and 28% aa sequence identity with IL‑1 ra, IL‑1 beta, IL‑36Ra/IL‑1F5, IL‑36 alpha/IL‑1F6, IL‑37/IL‑1F7, IL‑36 gamma/IL‑1F9 and IL‑1F10, respectively. Cells reported to express IL‑36 beta/IL‑1F8 include resting and activated monocytes and B cells (1, 4). The receptor for IL‑36 beta/IL‑1F8 is reported to be a combination of IL‑1 Rrp2 and IL‑1 RAcP (5). Recombinant IL‑36 beta/IL‑1F8, along with IL‑36 alpha/IL‑1F6 and IL‑36 gamma/IL‑1F9, has been shown to activate the pathway involving NF‑ kappaB and MAPK in an IL‑1 Rrp2 dependent manner.