期刊
ANGIOGENESIS
卷 16, 期 4, 页码 975-983出版社
SPRINGER
DOI: 10.1007/s10456-013-9367-4
关键词
alpha B-crystallin; Chaperone; ICAM-1; VCAM-1; E-selectin; NF-kappa B
资金
- Swedish Cancer Society
- Swedish Research Council
- Magnus Bergvall foundation
- Ake Wiberg foundation
- Svenska lakaresallskapet
- Clas Groschinsky foundation
- Lars Hierta foundation
- Harald and Greta Jeansson foundation
alpha B-crystallin is a small heat shock protein, which has pro-angiogenic properties by increasing survival of endothelial cells and secretion of vascular endothelial growth factor A. Here we demonstrate an additional role of alpha B-crystallin in regulating vascular function, through enhancing tumor necrosis factor alpha (TNF-alpha) induced expression of endothelial adhesion molecules involved in leukocyte recruitment. Ectopic expression of alpha B-crystallin in endothelial cells increases the level of E-selectin expression in response to TNF-alpha, and enhances leukocyte-endothelial interaction in vitro. Conversely, TNF-alpha-induced expression of intercellular adhesion molecule 1, vascular cell adhesion molecule 1 and E-selectin is markedly inhibited in endothelial cells isolated from alpha B-crystallin-deficient mice. This is associated with elevated levels of I kappa B in alpha B-crystallin deficient cells and incomplete degradation upon TNF-alpha stimulation. Consistent with this, endothelial adhesion molecule expression is reduced in inflamed vessels of alpha B-crystallin deficient mice, and leukocyte rolling velocity is increased. Our data identify alpha B-crystallin as a new regulator of leukocyte recruitment, by enhancing pro-inflammatory nuclear factor kappa B-signaling and endothelial adhesion molecule expression during endothelial activation.
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