Regulation of vascular cell adhesion molecule-1 expression by IL-4 and TNF-alpha in cultured endothelial cells.
Open Access
- 1 January 1995
- journal article
- Published by American Society for Clinical Investigation in JCI Insight
- Vol. 95 (1), 264-271
- https://doi.org/10.1172/jci117650
Abstract
Interaction between vascular cell adhesion molecule-1 (VCAM-1) on endothelial cells and alpha 4 integrins on leukocytes is thought to mediate the selective recruitment of eosinophils and lymphocytes that occurs in allergic diseases. IL-4 is associated with allergic conditions, and it has been shown to selectively increase expression of VCAM-1 on endothelial cells in vivo, suggesting that it could be responsible for VCAM-1 expression in allergic disease. Using a combination of immunofluorescence, flow cytometry, and Northern analysis, we compared the effect of TNF-alpha and IL-4 on VCAM-1 expression. TNF-alpha is also associated with allergic diseases, and it rapidly increases transcription of the VCAM-1 gene. The effect of IL-4 was relatively modest with prolonged kinetics: VCAM-1 was not detected until 72 h after treatment with IL-4. However, when TNF-alpha and IL-4 were combined, there was a synergistic increase in VCAM-1 expression and a dramatic prolongation of the appearance of VCAM-1 on the cell surface. This synergy results from a combination of transcriptional activation by TNF-alpha and the stabilization of resulting transcripts by IL-4. We propose that IL-4 allows subthreshold concentrations of TNF-alpha (concentrations that would not normally activate expression of adhesion molecules on the endothelium) to selectively increase VCAM-1 expression and to prolong its appearance on the surface of cells in allergic disease.Keywords
This publication has 55 references indexed in Scilit:
- Traffic signals for lymphocyte recirculation and leukocyte emigration: The multistep paradigmCell, 1994
- Expression of endothelial and leukocyte adhesion molecules intercellular adhesion molecule-1, E-selectin, and vascular cell adhesion molecule-1 in the bronchial mucosa in steady-state and allergen-induced asthmaJournal of Allergy and Clinical Immunology, 1993
- Induction of human IgE synthesis in B cells by mast cells and basophilsNature, 1993
- Transcription Factors in Lymphoid DevelopmentAnnals of the New York Academy of Sciences, 1993
- The potential role of tumour necrosis factor a in asthmaClinical and Experimental Allergy, 1993
- Endothelial-Leukocyte Adhesion MoleculesAnnual Review of Immunology, 1993
- Interleukin (IL) 4 differentially regulates monocyte IL-1 family gene expression and synthesis in vitro and in vivo.The Journal of Experimental Medicine, 1993
- Interleukin 4 and Tumour Necrosis Factor α Induce Different Adhesion Pathways in Endothelial Cells for the Binding of Peripheral Blood LymphocytesScandinavian Journal of Immunology, 1992
- 11–4 Decreases IFN‐γ‐Induced Endothelial ICAM‐1 Expression by a Transcriptional MechanismScandinavian Journal of Immunology, 1992
- Predominant TH2-like Bronchoalveolar T-Lymphocyte Population in Atopic AsthmaNew England Journal of Medicine, 1992