Recombinant Human IL-36 alpha/IL-1F6 Protein

Human interleukin‑36 alpha [IL‑36 alpha; previously IL‑1F6 and also FIL‑1 epsilon (epsilon)] 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‑37/IL‑1F7, IL‑36 beta/IL‑1F8, IL‑36 gamma/IL‑1F9 and IL‑1F10 (4, 6). All family members show a 12 beta‑strand, beta‑trefoil configuration, and all family members are believed to have arisen from a common ancestral gene that has undergone multiple duplications (4). IL‑36 alpha/IL‑1F6 is synthesized as a 158 amino acid (aa) protein that contains no signal sequence, no prosegment and no potential N‑linked glycosylation site(s) (1 ‑ 3). It appears to be actively secreted (1). When found in cell lysate, it presents as an 18 kDa monomer (2). Human to mouse, full length IL‑1F6 has 54% aa identity. Within the family, IL‑1F6 is 30% aa identical to IL‑1ra, and 27%, 31%, 36%, 46%, 57% and 28% aa identical to IL‑1 beta, IL‑36Ra/IL‑1F5, IL‑37/IL‑1F7, IL‑36 beta/IL‑1F8, IL‑36 gamma/IL‑1F9 and IL‑1F10, respectively. Cells reported to express IL‑36 alpha/IL‑1F6 include monocytes, B cells and T cells (1, 4). Notably, IL‑36 alpha/IL‑1F6 is the only novel IL‑1 family member found to be expressed on T cells. The receptor for IL‑36 alpha/IL‑1F6 is reported to be a combination of IL‑1 Rrp2 and IL‑1 RAcP (5). Recombinant IL‑36 alpha/IL‑1F6, along with IL‑36 beta/IL‑1F8 and IL‑36 gamma/IL‑1F9, has been shown to act as an agonist by activating the pathway involving NF‑ kappaB and MAPK in an IL‑1 Rrp2 dependent manner. This suggests that IL‑36 alpha/IL‑1F6 may signal in a similar fashion to IL‑1 and IL‑18 in having a binding receptor which upon ligation, recruits a second receptor as a signaling component, forming an active heterodimeric receptor complex.