Funding sources The study was supported by grants from the Dowling family, Epiderm Research and the Sydney Children’s Hospital Foundation.
Hypoxia regulates the production and activity of glucose transporter-1 and indoleamine 2,3-dioxygenase in monocyte-derived endothelial-like cells: possible relevance to infantile haemangioma pathogenesis
Version of Record online: 28 JAN 2011
© 2011 The Authors. BJD © 2011 British Association of Dermatologists
British Journal of Dermatology
Volume 164, Issue 2, pages 308–315, February 2011
How to Cite
Herbert, A., Ng, H., Jessup, W., Kockx, M., Cartland, S., Thomas, S.R., Hogg, P.J. and Wargon, O. (2011), Hypoxia regulates the production and activity of glucose transporter-1 and indoleamine 2,3-dioxygenase in monocyte-derived endothelial-like cells: possible relevance to infantile haemangioma pathogenesis. British Journal of Dermatology, 164: 308–315. doi: 10.1111/j.1365-2133.2010.10086.x
Conflicts of interest None declared.
- Issue online: 28 JAN 2011
- Version of Record online: 28 JAN 2011
- Accepted manuscript online: 7 OCT 2010 02:55PM EST
- Accepted for publication 27 September 2010
Background Infantile haemangioma (IH) may present as a precursor area of pallor prior to the initial proliferative phase, which implies that the early lesion may be hypoxic.
Objectives To examine the effect of hypoxia on the expression and activity of two key molecular markers of IH, glucose transporter-1 (GLUT1) and indoleamine 2,3-dioxygenase (IDO).
Methods IH endothelial cells express both haematopoietic and endothelial cell markers. CD14+ monocyte-derived endothelial-like cells have been employed in the study of IH and is the cell type used in this study.
Results GLUT1 transcript, protein and activity levels were strongly induced by hypoxia and remained elevated following 2 days of normoxic recovery. IDO transcript levels were not affected by hypoxia, although IDO protein level was reduced fivefold and IDO activity > 100-fold following 2 days of hypoxia. The protein and activity levels returned to normal following 2 days of normoxic recovery.
Conclusions The findings link the tissue hypoxia that precedes lesion development and the expression and/or activity of two key IH proteins. The early hypoxic insult may contribute to the elevated GLUT1 levels in IH lesions, while the very low IDO activity during the hypoxic phase may promote activation of immune cells in the lesion, which release cytokines that trigger IDO expression and activity and entry into the proliferative phase. Interestingly, IH lesion development shares some common features with ischaemia-reperfusion injury.