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

Mouse  interleukin‑36 alpha [IL‑36 alpha; previously IL‑1F6 and also named FIL‑1 epsilon (epsilon)] is a member of the IL‑1 family of proteins (1 ‑ 3, 7). 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, 7). 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 160 amino acid (aa) protein that contains no signal sequence, no prosegment and no potential N‑linked glycosylation site(s) (2, 5). It appears to be actively secreted (1). When found in cell lysates, it presents as an 18 kDa monomer (2). Mouse to human, full length IL‑36 alpha/IL‑1F6 has 54% aa identity. Within the family, IL‑36 alpha/IL‑1F6 is 29% aa identical to IL‑1ra, and 32%, 32%, 34%, 41%, and 28% aa identical to IL‑1 beta, IL‑36Ra/IL‑1F5, 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 (6). 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 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.