IL-36 gamma [previously called IL-1F9, IL-1 epsilon (epsilon), and IL-1H1] is a member of the IL-1 family which includes IL- 1 beta, IL- 1 alpha, IL- 1ra, IL- 18, IL- 36 Ra (IL- 1F5), IL-36 alpha (IL- 1F6), IL- 36 beta (IL- 1F8), IL- 37 (IL- 1F7) and IL-1F10. All family members show a 12 beta -strand, beta -trefoil configuration, and are believed to have arisen from a common ancestral gene. IL- 36 gamma is an 18- 22 kDa, 169 amino acid intracellular and secreted protein that contains no signal sequence, no prosegment and no potential N-linked glycosylation sites. Human IL- 36 gamma (aa 18- 169) shares 58%, 59%, 68% and 69% aa sequence identity with mouse, rat, bovine and equine IL- 36 gamma, respectively, and 23- 57% aa sequence identity with other family members. 134 aa isoform missing aa 19- 53 has been reported. Highest levels of IL- 36 gamma are produced by Langerhans cells, keratinocytes, and stomach Chief cells and parietal cells; these cells contribute to first-line defense against pathogens in the skin, lungs and digestive tract. Its expression is induced by LPS treatment of monocytes, and by IL- alpha / beta, IL- 17 or TNF- alpha treatment of keratinocytes and bronchial epithelia. Skin IL-36 gamma expression is increased in contact hypersensitivity and psoriasis. It is elevated in inflammatory disorders of the lung (such as asthma) and viral infections. Lung IL- 36 gamma and other IL- 36 proteins contribute to neutrophil influx. The receptor for IL-36 gamma is a combination of IL- 1 Rrp2, mainly found in epithelia and keratinocytes, and the widely expressed IL- 1 RAcP. IL- 36 alpha,beta and gamma all activate NF- kappa B and MAPK pathways in an IL- 1 Rrp2 dependent manner, and IL- 36 gamma induces production of inflammatory cytokines and chemokines such as CXCL8/IL- 8.
