title: Soluble interleukin-6 receptor alpha inhibits the cytokine-Induced fractalkine/CX3CL1 expression in human vascular endothelial cells in culture.
abstract: Soluble form of IL-6 receptor alpha (sIL-6R) is known to serve as an agonist, without exogenous IL-6, on endothelial cells which do not express IL-6R but have only IL-6 receptor beta chain, gp130. We investigated the effect of sIL-6R on fractalkine expression in human umbilical vein endothelial cells (HUVECs) in culture. sIL-6R markedly inhibited HUVEC fractalkine/CX3CL1 expression induced by interleukin (IL)-1alpha, tumor necrosis factor (TNF)-alpha, or interferon (IFN)-gamma. IL-1alpha-induced fractalkine expression was inhibited by sIL-6R in time- and concentration-dependent manners. The experiment using actinomycin D indicated that sIL-6R lowered the stability of fractalkine mRNA. The inhibitory effect of sIL-6R was reversed by anti-gp130 neutralizing antibody. sIL-6R inhibited adhesion of mononuclear cells (MNCs) to HUVEC monolayers stimulated with IFN-gamma, but it did not inhibit the adhesion to monolayers stimulated with IL-1alpha. MNC chemotactic activity of conditioned medium of HUVEC stimulated with IL-1alpha or IFN-gamma was inhibited by co-treatment with sIL-6R. sIL-6R may play a regulatory role in immune responses by modulating the interaction between leukocytes and the vascular endothelium.
authors.affiliation: Department of Dentistry and Oral Surgery, Hirosaki University School of Medicine, Hirosaki, 036-8562, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Matsumiya
authors.forename: T
authors.initials: T
authors.lastname: Imaizumi
authors.forename: K
authors.initials: K
authors.lastname: Fujimoto
authors.forename: X
authors.initials: X
authors.lastname: Cui
authors.forename: T
authors.initials: T
authors.lastname: Shibata
authors.forename: W
authors.initials: W
authors.lastname: Tamo
authors.forename: M
authors.initials: M
authors.lastname: Kumagai
authors.forename: K
authors.initials: K
authors.lastname: Tanji
authors.forename: H
authors.initials: H
authors.lastname: Yoshida
authors.forename: H
authors.initials: H
authors.lastname: Kimura
authors.forename: K
authors.initials: K
authors.lastname: Satoh
mesh_terms: D002448:Cell Adhesion / Q000187:drug effects / Q000276:immunology; D002478:Cells, Cultured / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D054428:Chemokine CX3CL1; D020523:Chemokines, CX3C / Q000235:genetics*; D002633:Chemotaxis / Q000187:drug effects / Q000276:immunology; D002634:Chemotaxis, Leukocyte / Q000187:drug effects / Q000502:physiology*; D058966:Contactins; D017077:Culture Media, Conditioned / Q000494:pharmacology; D016207:Cytokines / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects / Q000276:immunology; D006801:Humans; D007249:Inflammation / Q000276:immunology* / Q000378:metabolism; D015850:Interleukin-6 / Q000276:immunology / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics*; D019006:Neural Cell Adhesion Molecules / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D019947:Receptors, Interleukin-6 / Q000378:metabolism*
chemical_list: C515538:CX3CL1 protein, human; D054428:Chemokine CX3CL1; D020523:Chemokines, CX3C; D058966:Contactins; D017077:Culture Media, Conditioned; D016207:Cytokines; D015850:Interleukin-6; D008565:Membrane Proteins; D019006:Neural Cell Adhesion Molecules; D012333:RNA, Messenger; D019947:Receptors, Interleukin-6