Recombinant Mouse Interleukin-36 alpha protein (Il36a)

Function

Cytokine that binds to and signals through the IL1RL2/IL-36R receptor which in turn activates NF-kappa-B and MAPK signaling pathways in target cells linked to a pro-inflammatory response. Part of the IL-36 signaling system that is thought to be present in epithelial barriers and to take part in local inflammatory response; similar to the IL-1 system with which it shares the coreceptor IL1RAP. Seems to be involved in skin inflammatory response by acting on keratinocytes, dendritic cells and indirectly on T-cells to drive tissue infiltration, cell maturation and cell proliferation. Induces the production of pro-inflammatory cytokines, including IL-12, Il-1 beta, IL-6, TNF and IL-23 in bone marrow-derived dendritic cells (BMDCs). Involved in dendritic cell maturation by stimulating the surface expression of CD80, CD86 and MHC class II. Induces the production of IFN-gamma, IL-4 and IL-17 by cultured CD4(+) T-cells and splenocytes. May play a role in pro-inflammatory effects in the lung: induces the expression of CXCL1 and CXCL2 in the lung, and the expression of TNF, IL-36c, IL-1A, IL-1B, CXCL1 and CXCL2 in isolated splenic CD11c(+) alveolar macrophages. May be involved in T-cell maturation by stimulating the surface expression of CD40 and modestly CD80 and CD86 in splenic CD11c(+) cells. May be involved in CD4(+) T-cell proliferation. Induces NF-kappa B activation in macrophages

Subcellular Location

Cytoplasm; Secreted

Tissue Specificity

Highly expressed in embryonic tissue and in tissues containing epithelial cells. Elevated expression levels are detected in chronic kidney disease; expressed inepithelia from the distal convoluted tubules (DCTs) to the cortical collecting ducts (CCDs) in single nephrons (at protein level)

Subunit

Interacts with TMED10; the interaction mediates the translocation from the cytoplasm into the ERGIC (endoplasmic reticulum-Golgi intermediate compartment) and thereby secretion

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• Debets R. et al. Two novel IL-1 family members, IL-1 delta and IL-1 epsilon, function as an antagonist and agonist of NF-kappa B activation through the orphan IL-1 receptor-related protein 2. — J. Immunol. (2001)
• Carninci P. et al. The transcriptional landscape of the mammalian genome. — Science (2005)
• Ichii O. et al. Local overexpression of interleukin-1 family, member 6 relates to the development of tubulointerstitial lesions. — Lab. Invest. (2010)
• Vigne S. et al. IL-36R ligands are potent regulators of dendritic and T cells. — Blood (2011)
• Towne J.E. et al. Interleukin-36 (IL-36) ligands require processing for full agonist (IL-36alpha, IL-36beta, and IL-36gamma) or antagonist (IL-36Ra) activity. — J. Biol. Chem. (2011)
• Carrier Y. et al. Inter-regulation of Th17 cytokines and the IL-36 cytokines in vitro and in vivo: implications in psoriasis pathogenesis. — J. Invest. Dermatol. (2011)
• Ramadas R.A. et al. IL-36alpha exerts pro-inflammatory effects in the lungs of mice. — PLoS ONE (2012)