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Ibuprofen inhibits pyrogen-dependent expression of VCAM-1 and ICAM-1 on human endothelial cells.
- Source :
-
Life sciences [Life Sci] 1996; Vol. 58 (23), pp. 2167-81. - Publication Year :
- 1996
-
Abstract
- Leukocyte adhesion and transmigration through the endothelial cell (EC) layer plays a crucial role in inflammation. IL-1 alpha and TNF alpha increase EC-adhesiveness for leukocytes by stimulating surface expression of ICAM-1 (intercellular adhesion molecule 1, CD54), VCAM-1 (vascular cell adhesion molecule 1, CD106) and E-selectin (CD62E). In this study, the effects of ibuprofen on IL-1 alpha and TNF alpha-induced expression of ICAM-1, VCAM-1 and E-selectin on cultured human umbilical vein EC (HUVEC) were analyzed. Exposure to IL-1 alpha or TNF alpha resulted in an increased expression of VCAM-1, ICAM-1, and E-selectin. Ibuprofen was identified as a potent inhibitor of IL-1 alpha and TNF alpha-induced surface expression of VCAM-1 and a less potent inhibitor of pyrogen-induced expression of ICAM-1, whereas no effect on E-selectin was found. The effects of ibuprofen on VCAM-1 expression were dose-dependent (IC50 [IL-1 alpha]: 0.5 mM; IC50 [TNF alpha]: 0.5 mM) and time-dependent with maximum responses observed after 18 h. Moreover, ibuprofen abrogated pyrogen-dependent adhesion of leukocytes to HUVEC. Ibuprofen also inhibited VCAM-1 mRNA expression in pyrogen activated EC. VCAM-1-downregulation on EC by ibuprofen may contribute to the anti-inflammatory actions of the drug.
- Subjects :
- Base Sequence
Cell Adhesion
Cell Membrane metabolism
Cells, Cultured
Cytokines pharmacology
DNA Primers chemistry
E-Selectin metabolism
Flow Cytometry
Gene Expression drug effects
Humans
Interleukin-1 metabolism
Leukocytes, Mononuclear cytology
Molecular Sequence Data
Neutrophils cytology
RNA, Messenger genetics
Radioligand Assay
Tumor Necrosis Factor-alpha pharmacology
Endothelium, Vascular metabolism
Ibuprofen pharmacology
Intercellular Adhesion Molecule-1 metabolism
Pyrogens pharmacology
Vascular Cell Adhesion Molecule-1 metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0024-3205
- Volume :
- 58
- Issue :
- 23
- Database :
- MEDLINE
- Journal :
- Life sciences
- Publication Type :
- Academic Journal
- Accession number :
- 8649201
- Full Text :
- https://doi.org/10.1016/0024-3205(96)00210-x