Upregulation of TNF-α-induced ICAM-1 surface expression by adenylate cyclase-dependent pathway in human endothelial cells
Version of Record online: 5 AUG 2004
Copyright © 2004 Wiley-Liss, Inc.
Journal of Cellular Physiology
Volume 202, Issue 2, pages 434–441, February 2005
How to Cite
Bernot, D., Peiretti, F., Canault, M., Juhan-Vague, I. and Nalbone, G. (2005), Upregulation of TNF-α-induced ICAM-1 surface expression by adenylate cyclase-dependent pathway in human endothelial cells. J. Cell. Physiol., 202: 434–441. doi: 10.1002/jcp.20134
- Issue online: 23 NOV 2004
- Version of Record online: 5 AUG 2004
- Manuscript Accepted: 27 APR 2004
- Manuscript Received: 15 MAR 2004
- Inserm (Paris, France)
- Fondation pour la Recherche Médicale (Paris)
The level of adhesion molecules expressed at the endothelial cell surface is critical in the control of inflammation. Adenylate cyclase (AC) activity allowing cyclic adenosine monophosphate (cAMP) production can modulate the inflammatory process. We investigated the AC-dependent modulation of ICAM-1 surface expression in human umbilical venous endothelial cells (HUVEC). Pretreatment of HUVEC with forskolin significantly upregulated tumor necrosis factor alpha (TNF-α)- and interleukin-1 alpha (IL1-α)-induced ICAM-1 surface expression exclusively after a prolonged time of incubation with forskolin (at least 7–8 h). A poorly metabolizable analog of cAMP, dibutyryl-cAMP, mimicked forskolin effect on ICAM-1 surface expression. Protein kinase A (PKA) inhibitor H89 prevented forskolin effect on ICAM-1 surface expression. Upregulation of ICAM-1 surface level occurred through the increase in its mRNA levels and also to a subsequent activation of ICAM-1 intracellular trafficking towards cell surface. Stimulation by agonists of β-adrenergic receptors did not alter the TNF-α-induced ICAM-1 surface expression. Pretreatment of HUVEC with pertussis toxin, which is known to activate AC through Giα inhibition, upregulated mRNA levels and surface expression of ICAM-1 induced by TNF-α. This effect was serum-dependent, since ICAM-1 expression was no more upregulated by pertussis toxin in cells cultured in 1% instead of 20% serum-enriched medium. However, forskolin treatment of HUVEC did not modify their overall adhesive properties. In conclusion, a persistent cAMP level elevation activating PKA is able to enhance ICAM-1 expression at the cell surface of endothelial cells placed under pro-inflammatory conditions. Combination of activation of gene transcription and membrane targeting may account for this augmentation. © 2004 Wiley-Liss, Inc.