Thromboxane A{sub 2} increases endothelial permeability through upregulation of interleukin-8
- School of Dentistry and Research Institute for Oral Biotechnology, Pusan National University, Yangsan 626-870 (Korea, Republic of)
- Medical Research Center for Ischemic Tissue Regeneration and School of Medicine, Pusan National University, Yangsan 626-870 (Korea, Republic of)
- Department of Molecular Biology, Pusan National University, Pusan 609-735 (Korea, Republic of)
Thromboxane A{sub 2} (TXA{sub 2}), a major prostanoid formed from prostaglandin H{sub 2} by thromboxane synthase, is involved in the pathogenesis of a variety of vascular diseases. In this study, we report that TXA{sub 2} mimetic U46619 significantly increases the endothelial permeability both in vitro and in vivo. U46619 enhanced the expression and secretion of interleukin-8 (IL-8), a major inducer of vascular permeability, in endothelial cells. Promoter analysis showed that the U46619-induced expression of IL-8 was mainly regulated by nuclear factor-{kappa}B (NF-{kappa}B). U46619 induced the activation of NF-{kappa}B through I{kappa}B kinase (IKK) activation, I{kappa}B phosphorylation and NF-{kappa}B nuclear translocation. Furthermore, the inhibition of IL-8 or blockade of the IL-8 receptor attenuated the U46619-induced endothelial cell permeability by modulating the cell-cell junctions. Overall, these results suggest that U46619 promotes vascular permeability through the production of IL-8 via NF-{kappa}B activation in endothelial cells.
- OSTI ID:
- 22202670
- Journal Information:
- Biochemical and Biophysical Research Communications, Vol. 397, Issue 3; Other Information: Copyright (c) 2010 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); ISSN 0006-291X
- Country of Publication:
- United States
- Language:
- English
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