PMID:18787100

Citation	Küchler, AM, Pollheimer, J, Balogh, J, Sponheim, J, Manley, L, Sorensen, DR, De Angelis, PM, Scott, H and Haraldsen, G (2008) Nuclear interleukin-33 is generally expressed in resting endothelium but rapidly lost upon angiogenic or proinflammatory activation. Am. J. Pathol. 173:1229-42
Abstract	Interleukin (IL)-33 is a novel member of the IL-1 family of cytokines that promotes Th2 responses in lymphocytes as well as the activation of both mast cells and eosinophils via the ST2 receptor. Additionally, IL-33 has been proposed to act as a chromatin-associated transcriptional regulator in both endothelial cells of high endothelial venules and chronically inflamed vessels. Here we show that nuclear IL-33 is expressed in blood vessels of healthy tissues but down-regulated at the earliest onset of angiogenesis during wound healing; in addition, it is almost undetectable in human tumor vessels. Accordingly, IL-33 is induced when cultured endothelial cells reach confluence and stop proliferating but is lost when these cells begin to migrate. However, IL-33 expression was not induced by inhibiting cell cycle progression in subconfluent cultures and was not prevented by antibody-mediated inhibition of VE-cadherin. Conversely, IL-33 knockdown did not induce detectable changes in either expression levels or the cellular distribution of either VE-cadherin or CD31. However, activation of endothelial cell cultures with either tumor necrosis factor-alpha or vascular endothelial growth factor and subcutaneous injection of these cytokines led to a down-regulation of vascular IL-33, a response consistent with both its rapid down-regulation in wound healing and loss in tumor endothelium. In conclusion, we speculate that the proposed transcriptional repressor function of IL-33 may be involved in the control of endothelial cell activation.
Links	PubMed PMC2543089 Online version:10.2353/ajpath.2008.080014
Keywords	Animals; Blood Vessels/drug effects; Blood Vessels/metabolism; Cell Count; Cell Movement/drug effects; Cell Nucleus/drug effects; Cell Nucleus/metabolism; Cells, Cultured; Cytokines/pharmacology; Down-Regulation/drug effects; Endothelium/drug effects; Endothelium/metabolism; Endothelium/pathology; Female; Health; Humans; Inflammation/metabolism; Interleukin-33; Interleukins/metabolism; Neoplasms/metabolism; Neoplasms/pathology; Neovascularization, Pathologic/metabolism; Rats; Tumor Necrosis Factor-alpha/pharmacology; Vascular Endothelial Growth Factor A/pharmacology; Wound Healing/drug effects
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
HUMAN:IL33		GO:0005634: nucleus	ECO:0000314:		C		Figure 1 shows expression of Il33 in the nuclei of Normal human tissue. Figure 2F shows expression of Il33 in the nucleus of superconfluent cells	complete CACAO 11787

References

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