title: Co-expression of ICAM-1, VCAM-1, ELAM-1 and Hsp60 in human arterial and venous endothelial cells in response to cytokines and oxidized low-density lipoproteins.
abstract: T-cells and monocytes are the first cells infiltrating the arterial intima during the early stages of atherogenesis. Recently our laboratory has provided evidence that T-cells isolated from atherosclerotic intima reacts against heat shock protein 60 (Hsp60). Transmigration of activated T-cells into the intima is mediated by adhesion molecules (ICAM-1; VCAM-1; ELAM-1) expressed on activated endothelial cells. Here we studied the potential of cytokines (TNF-alpha, IFN-gamma, IL-1). Escherichia coli lipopolysaccharide (LPS), native and oxidized low-density lipoprotein (LDL; oxLDL) and high temperature to induce adhesion molecules as well as Hsp60 and Hsp70 expression in human endothelial cells (EC). On Northern blots, a strong signal for ICAM-1, VCAM-1 and ELAM-1 was detected after 4 h, which thereafter declined, but did not reach the basal level of untreated control cells. Heat shock induced the expression of Hsp60 and Hsp70 but not of adhesion molecules. EC were cultivated in serum-free medium, which led to the expression of adhesion molecule transcripts. Addition of LDL or oxLDL to these ECs did not alter the expression of these transcripts. The production of adhesion molecule proteins was analysed by flow cytometry. In human venous endothelial cells (HVEC) and human arterial endothelial cells (HAEC) ICAM-1 and VCAM-1 production was permanently highly induced, whereas the high level of ELAM-1 production at 4 h disappeared after 24 h. Furthermore, only HAEC, but not HVEC, produced ICAM-1, VCAM-1 and ELAM-1 after stress by moderately and highly oxLDL. LDL and oxLDL did not induce the production of Hsp60 and Hsp70. The present study demonstrates the co-expression of Hsp60 and adhesion molecules in arterial and venous EC in response to cytokine and LPS exposure, and that oxLDL is an efficient inducer of adhesion molecules in arterial EC and not in venous EC. These features provide the prerequisites for a cellular immune reaction against Hsp60 expressed by stressed EC in the initial stages of atherosclerosis.
authors.affiliation: Institute for Biomedical Aging Research, Austrian Academy of Sciences, Innsbruck, Austria.
authors.forename: A
authors.initials: A
authors.lastname: Amberger
authors.forename: C
authors.initials: C
authors.lastname: Maczek
authors.forename: G
authors.initials: G
authors.lastname: Jürgens
authors.forename: D
authors.initials: D
authors.lastname: Michaelis
authors.forename: G
authors.initials: G
authors.lastname: Schett
authors.forename: K
authors.initials: K
authors.lastname: Trieb
authors.forename: T
authors.initials: T
authors.lastname: Eberl
authors.forename: S
authors.initials: S
authors.lastname: Jindal
authors.forename: Q
authors.initials: Q
authors.lastname: Xu
authors.forename: G
authors.initials: G
authors.lastname: Wick
mesh_terms: D015703:Antigens, CD / Q000032:analysis / Q000235:genetics*; D001161:Arteriosclerosis / Q000378:metabolism / Q000503:physiopathology; D015152:Blotting, Northern; D002478:Cells, Cultured; D018834:Chaperonin 60 / Q000032:analysis / Q000235:genetics*; D016207:Cytokines / Q000494:pharmacology*; D019040:E-Selectin / Q000032:analysis / Q000235:genetics; D004730:Endothelium, Vascular / Q000737:chemistry / Q000166:cytology* / Q000187:drug effects; D004731:Endotoxins / Q000494:pharmacology; D005263:Femoral Artery / Q000166:cytology; D005434:Flow Cytometry; D015870:Gene Expression / Q000187:drug effects; D018840:HSP70 Heat-Shock Proteins / Q000032:analysis / Q000235:genetics; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000032:analysis / Q000235:genetics; D008077:Lipoproteins, LDL / Q000378:metabolism / Q000494:pharmacology*; D010084:Oxidation-Reduction; D012333:RNA, Messenger / Q000032:analysis; D012501:Saphenous Vein / Q000166:cytology; D019010:Vascular Cell Adhesion Molecule-1 / Q000032:analysis / Q000235:genetics
chemical_list: D015703:Antigens, CD; D018834:Chaperonin 60; D016207:Cytokines; D019040:E-Selectin; D004731:Endotoxins; D018840:HSP70 Heat-Shock Proteins; D008077:Lipoproteins, LDL; D012333:RNA, Messenger; D019010:Vascular Cell Adhesion Molecule-1; C099252:oxidized low density lipoprotein; D018799:Intercellular Adhesion Molecule-1