6hpi

Structural highlights

Function

IL36A_HUMAN 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. In cultured keratinocytes induces the expression of macrophage, T-cell, and neutrophil chemokines, such as CCL3, CCL4, CCL5, CCL2, CCL17, CCL22, CL20, CCL5, CCL2, CCL17, CCL22, CXCL8, CCL20 and CXCL1, and the production of proinflammatory cytokines such as TNF-alpha, IL-8 and IL-6. In cultured monocytes upregulates expression of IL-1A, IL-1B and IL-6. In myeloid dendritic cells involved in cell maturation by upregulating surface expression of CD83, CD86 and HLA-DR. In monocyte-derived dendritic cells facilitates dendritic cell maturation and drives T-cell proliferation. May play a role in proinflammatory effects in the lung.^{[1] [2] [3] [4]}

See Also

• Interleukin 3D structures

References

1. ↑ Towne JE, Garka KE, Renshaw BR, Virca GD, Sims JE. Interleukin (IL)-1F6, IL-1F8, and IL-1F9 signal through IL-1Rrp2 and IL-1RAcP to activate the pathway leading to NF-kappaB and MAPKs. J Biol Chem. 2004 Apr 2;279(14):13677-88. doi: 10.1074/jbc.M400117200. Epub 2004 , Jan 20. PMID:14734551 doi:http://dx.doi.org/10.1074/jbc.M400117200
2. ↑ Carrier Y, Ma HL, Ramon HE, Napierata L, Small C, O'Toole M, Young DA, Fouser LA, Nickerson-Nutter C, Collins M, Dunussi-Joannopoulos K, Medley QG. Inter-regulation of Th17 cytokines and the IL-36 cytokines in vitro and in vivo: implications in psoriasis pathogenesis. J Invest Dermatol. 2011 Dec;131(12):2428-37. doi: 10.1038/jid.2011.234. Epub 2011, Sep 1. PMID:21881584 doi:http://dx.doi.org/10.1038/jid.2011.234
3. ↑ Towne JE, Renshaw BR, Douangpanya J, Lipsky BP, Shen M, Gabel CA, Sims JE. 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 Dec 9;286(49):42594-602. doi: 10.1074/jbc.M111.267922. Epub, 2011 Sep 29. PMID:21965679 doi:http://dx.doi.org/10.1074/jbc.M111.267922
4. ↑ Foster AM, Baliwag J, Chen CS, Guzman AM, Stoll SW, Gudjonsson JE, Ward NL, Johnston A. IL-36 promotes myeloid cell infiltration, activation, and inflammatory activity in skin. J Immunol. 2014 Jun 15;192(12):6053-61. doi: 10.4049/jimmunol.1301481. Epub 2014 , May 14. PMID:24829417 doi:http://dx.doi.org/10.4049/jimmunol.1301481