title: Ibuprofen inhibits pyrogen-dependent expression of VCAM-1 and ICAM-1 on human endothelial cells.
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.
authors.affiliation: Clin. Inst. of Med., Univ. Vienna, Austria.
authors.forename: S
authors.initials: S
authors.lastname: Kapiotis
authors.forename: G
authors.initials: G
authors.lastname: Sengoelge
authors.forename: W R
authors.initials: WR
authors.lastname: Sperr
authors.forename: M
authors.initials: M
authors.lastname: Baghestanian
authors.forename: P
authors.initials: P
authors.lastname: Quehenberger
authors.forename: D
authors.initials: D
authors.lastname: Bevec
authors.forename: S R
authors.initials: SR
authors.lastname: Li
authors.forename: E J
authors.initials: EJ
authors.lastname: Menzel
authors.forename: A
authors.initials: A
authors.lastname: Mühl
authors.forename: D
authors.initials: D
authors.lastname: Zapolska
authors.forename: I
authors.initials: I
authors.lastname: Virgolini
authors.forename: P
authors.initials: P
authors.lastname: Valent
authors.forename: W
authors.initials: W
authors.lastname: Speiser
mesh_terms: D001483:Base Sequence; D002448:Cell Adhesion; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D016207:Cytokines / Q000494:pharmacology; D017931:DNA Primers / Q000737:chemistry; D019040:E-Selectin / Q000378:metabolism; D004730:Endothelium, Vascular / Q000378:metabolism*; D005434:Flow Cytometry; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007052:Ibuprofen / Q000494:pharmacology*; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism*; D007375:Interleukin-1 / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000166:cytology; D008969:Molecular Sequence Data; D009504:Neutrophils / Q000166:cytology; D011749:Pyrogens / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics; D011869:Radioligand Assay; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism*
chemical_list: D016207:Cytokines; D017931:DNA Primers; D019040:E-Selectin; D007375:Interleukin-1; D011749:Pyrogens; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D007052:Ibuprofen