Recombinant Human IL-36 beta/IL-1F8 (aa 5-157) Protein

Human interleukin‑36 beta [IL‑36 beta; previously IL‑1F8, FIL‑1 eta (eta) and IL‑1H2] is a member of the IL‑1 family of proteins that includes 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 (1 ‑ 6). All family members show a 12 beta‑stranded beta‑trefoil configuration, share up to 50% amino acid (aa) sequence identity, and are believed to have arisen from a common ancestral gene (3, 4). Two isoforms differ in their C‑terminal 70 aa (3). IL‑36 beta isoform 2 (IL‑36 beta2) is a 157 aa protein that, like IL‑1, lacks a signal sequence and prosegment, but can be actively secreted as well as intracellular (1). IL‑36 beta2 contains one potential N‑linked glycosylation site in its C‑terminus, while IL‑36 beta isoform 1 lacks potential N‑linked glycosylation sites and four of the conserved beta‑strands (1). Human IL‑36 beta2 shares 62%, 67%, 63% and 59% aa identity with the most similar isoform of mouse, canine, bovine and equine IL‑36 beta, respectively. It is agonistic, stimulating release of inflammatory mediators such as IL‑6 and IL‑8, and cytotoxic peptides such as beta‑defensins 2 and 3 that aid in defense against microbial pathogens (7 ‑ 10). The receptor for IL‑36 proteins is IL‑1 Rrp2, with IL‑1 RAcP as a coreceptor (7, 9). Antagonism of IL‑36 proteins by IL‑36Ra, which also binds IL‑1 Rrp2, has been shown by some investigators (5, 6). Skin keratinocytes express highest levels of IL‑36 proteins and their receptors, followed by epithelia in the esophagus, trachea and bronchae (7 ‑ 9). IL‑36 beta expression is increased in psoriatic skin and may play a role in pathogenesis of psoriasis (7, 8). IL‑36 beta is also expressed in resting and activated monocytes and B cells, synovial fibroblasts, neurons and glia, and is detectable in plasma and body fluids (1, 7, 9, 11). IL‑36 beta, along with IL‑36 alpha and IL‑36 gamma, is up‑regulated by IL‑1 alpha and TNF‑ alpha in keratinocytes, and has been shown to activate NF‑ kappaB and MAPK signaling pathways in an IL‑1 Rrp2‑dependent manner (7 ‑ 9). Full‑length recombinant IL‑36 proteins appear less active than their endogenous counterparts, but trimming of the N‑termini enhances their activity (9, 12).