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Upregulation of TNF-alpha-induced ICAM-1 surface expression by adenylate cyclase-dependent pathway in human endothelial cells.
- Source :
-
Journal of cellular physiology [J Cell Physiol] 2005 Feb; Vol. 202 (2), pp. 434-41. - Publication Year :
- 2005
-
Abstract
- 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-alpha)- and interleukin-1 alpha (IL1-alpha)-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 beta-adrenergic receptors did not alter the TNF-alpha-induced ICAM-1 surface expression. Pretreatment of HUVEC with pertussis toxin, which is known to activate AC through Gialpha inhibition, upregulated mRNA levels and surface expression of ICAM-1 induced by TNF-alpha. 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.<br /> (2004 Wiley-Liss, Inc.)
- Subjects :
- Cell Adhesion drug effects
Cells, Cultured
Colforsin pharmacology
Cyclic AMP biosynthesis
Cyclic AMP-Dependent Protein Kinases metabolism
Endothelial Cells physiology
GTP-Binding Protein alpha Subunits, Gi-Go antagonists & inhibitors
Humans
Intercellular Adhesion Molecule-1 genetics
RNA, Messenger metabolism
Umbilical Veins cytology
Up-Regulation
Adenylyl Cyclases physiology
Cell Membrane metabolism
Endothelial Cells drug effects
Endothelial Cells metabolism
Intercellular Adhesion Molecule-1 metabolism
Tumor Necrosis Factor-alpha pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 0021-9541
- Volume :
- 202
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Journal of cellular physiology
- Publication Type :
- Academic Journal
- Accession number :
- 15389590
- Full Text :
- https://doi.org/10.1002/jcp.20134