IL-36γ has proinflammatory effects on human endothelial cells.
Interleukin-36 cytokines are predominantly expressed by epithelial cells. Significant upregulation of epidermal IL-36 is now a recognised characteristic of psoriatic skin inflammation. IL-36 is known to induce inflammatory responses in dendritic cells, fibroblasts and epithelial cells. Although vascular alterations are a hallmark of psoriatic lesions and dermal endothelial cells are well known to play a critical role in skin inflammation, the effects of IL-36 on endothelial cells are unexplored. We here show that endothelial cells including dermal microvascular cells express a functionally active IL-36 receptor. Adhesion molecules VCAM-1 and ICAM-1 are upregulated by IL-36γ stimulation, and this is reversed by the presence of the endogenous IL-36 receptor antagonist. IL-36γ-stimulated endothelial cells secrete the proinflammatory chemokines IL-8, CCL2 and CCL20. Chemotaxis assays showed increased migration of T-cells following IL-36γ stimulation of endothelial cells. These results suggest a role for IL-36γ in the dermal vascular compartment, and it is likely to enhance psoriatic skin inflammation by activating endothelial cells and promoting leucocyte recruitment.
Centre for Skin Sciences, Faculty of Life Sciences, University of Bradford, Bradford, UK.
Charlie
C
Bridgewood
School of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds, UK.
Martin
M
Stacey
Leeds Institute of Rheumatic and Musculoskeletal Medicine (LIRMM), University of Leeds, Leeds, UK.
Adewonuola
A
Alase
Centre for Immunology and Infection, Hull York Medical School and Department of Biology, University of York, UK.
Dimitris
D
Lagos
School of Medical Sciences, University of Bradford, Bradford, UK.
Anne
A
Graham
Centre for Skin Sciences, Faculty of Life Sciences, University of Bradford, Bradford, UK.|Leeds Institute of Rheumatic and Musculoskeletal Medicine (LIRMM), University of Leeds, Leeds, UK.|National Institute of Health Research (NIHR) LMBRU, Chapel Allerton Hospital, Leeds, UK.
Miriam
M
Wittmann
D018932:Chemokine CCL2 / Q000378:metabolism; D054418:Chemokine CCL20 / Q000378:metabolism; D042783:Endothelial Cells / Q000378:metabolism*; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D007375:Interleukin-1 / Q000502:physiology*; D016209:Interleukin-8 / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism; D011565:Psoriasis / Q000378:metabolism; D018123:Receptors, Interleukin / Q000378:metabolism*; D013601:T-Lymphocytes / Q000502:physiology; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
C111835:CCL2 protein, human; C108355:CCL20 protein, human; C508606:CXCL8 protein, human; D018932:Chemokine CCL2; D054418:Chemokine CCL20; C508589:IL36G protein, human; D007375:Interleukin-1; D016209:Interleukin-8; D016328:NF-kappa B; D016755:Proto-Oncogene Proteins c-jun; D018123:Receptors, Interleukin; D019010:Vascular Cell Adhesion Molecule-1; C571244:interleukin-36 receptor, human; D018799:Intercellular Adhesion Molecule-1
IL-36; endothelial; inflammation; psoriasis; skin