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IL-4, but not tumor necrosis factor-alpha, increases endothelial cell adhesiveness for lymphocytes by activating a cAMP-dependent pathway.
- Source :
-
Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 1993 Jul 15; Vol. 151 (2), pp. 588-96. - Publication Year :
- 1993
-
Abstract
- IL-4 and TNF-alpha increase endothelial cell adhesiveness for PBL by promoting the expression of adhesion molecules. We investigated the intracellular cAMP involvement in the increased endothelial cell adhesivity induced by IL-4 or TNF-alpha. We showed that both IL-4 and TNF-alpha increased intracellular cAMP in endothelial cells (EC). Furthermore, dibutyryl-cAMP and forskolin (which increased intracellular cAMP) increased basic EC adhesivity for PBL. The co-stimulation of EC with cAMP elevating agents and TNF-alpha, but not IL-4, resulted in an additive increase in EC adhesiveness. 2',5' dideoxyadenosine, an inhibitor of adenylate cyclase, decreased PBL adhesion to IL-4- but not TNF-alpha-treated EC. Similarly, HA1004, a protein kinase A inhibitor, totally reversed the IL-4 but not TNF-alpha effect on EC adhesiveness, whereas H7, a protein kinase C inhibitor, did not antagonise cytokine-enhanced EC adhesivity. These results indicate that IL-4, but not TNF-alpha, uses a cAMP-dependent pathway to increase PBL adhesion. Furthermore, we showed that cAMP elevation in EC did not induce vascular cell adhesion molecule 1, the only identified adhesion molecule induced by IL-4, indicating that a rise in cAMP in EC promotes an as yet unidentified adhesion pathway. Our results show that IL-4 increases EC adhesiveness for PBL through activation of protein kinase A by promoting an unidentified adhesion pathway.
- Subjects :
- Cell Adhesion
Cell Adhesion Molecules analysis
Cell Adhesion Molecules physiology
Cells, Cultured
Endothelium, Vascular cytology
Humans
Intercellular Adhesion Molecule-1
Vascular Cell Adhesion Molecule-1
Cyclic AMP metabolism
Endothelium, Vascular drug effects
Interleukin-4 pharmacology
Lymphocytes physiology
Tumor Necrosis Factor-alpha pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 0022-1767
- Volume :
- 151
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Journal of immunology (Baltimore, Md. : 1950)
- Publication Type :
- Academic Journal
- Accession number :
- 7687617