Haraldsen´s group presents interesting findings concerning IL-33 - may be involved in the control of endothelial cell activation
Küchler AM, Pollheimer J, Balogh J, Sponheim J, Manley L, Sorensen DR, De Angelis PM, Scott H, Haraldsen G. Publish in Am J Pathol. 2008 Oct;173(4):1229-42.
“Nuclear interleukin-33 is generally expressed in resting endothelium
but rapidly lost upon angiogenic or proinflammatory activation.”
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.
