title: Activation of NF-kappa B and induction of vascular cell adhesion molecule-1 and intracellular adhesion molecule-1 expression in human glial cells by IL-1. Modulation by antioxidants.
abstract: The infiltration of leukocytes into the central nervous system is associated with many pathologic conditions of the brain. The mechanisms by which these immune cells can penetrate the blood-brain barrier and remain within the brain are not understood. However, elevated brain levels of the pro-inflammatory cytokine IL-1 appear to accompany pathogenesis. The present study provides the first evidence that IL-1 can induce the expression of adhesion molecules for leukocytes on glial cells and suggests a role for the transcription factor NF-kappa B in the induction process. Human rIL-1 alpha was found to induce the expression of the cell adhesion molecules, vascular cell adhesion molecule-1 (VCAM-1), and intercellular adhesion molecule-1 (ICAM-1) but not E-selectin in human 1321N1 astrocytoma. Both VCAM-1 and ICAM-1 were detectable from 3 h and remained sustained for up to 72 h. Induction was inhibited by the IL-1 receptor antagonist. IL-1 alpha was also shown to induce the expression of VCAM-1 and ICAM-1 in a receptor-dependent fashion in human A172 glioblastoma. Activation of the transcription factor NF-kappa B was also observed in 1321N1 astrocytoma in response to IL-1 alpha treatment and was similarly abolished by pretreatment of cells with antagonist. Activated NF-kappa B was apparent from 20 min and remained for up to 24 h. N-acetylcysteine (NAC) and pyrollidinedithiocarbamate (PDTC), which were shown to inhibit activation of NF-kappa B in Jurkat E6.1 lymphoblasts and EL4.NOB-1 thymoma, failed to block IL-1 activation of NF-kappa B in 1321N1 astrocytoma. However, both of these antioxidants demonstrated complex modulatory effects on the induction of cell adhesion molecule expression by IL-1. The induction of VCAM-1 but not of ICAM-1 proved susceptible to inhibition by both PDTC and NAC. The expression of adhesion molecules for leukocytes on glial cells in response to IL-1 may represent an important mechanism for retention of immune cells in the central nervous system that may be a prologue to inflammatory conditions in the brain.
authors.affiliation: Department of Biochemistry and Biotechnology Institute, Trinity College, University of Dublin, Ireland.
authors.forename: P N
authors.initials: PN
authors.lastname: Moynagh
authors.forename: D C
authors.initials: DC
authors.lastname: Williams
authors.forename: L A
authors.initials: LA
authors.lastname: O'Neill
mesh_terms: D000975:Antioxidants / Q000494:pharmacology; D001483:Base Sequence; D015815:Cell Adhesion Molecules / Q000096:biosynthesis*; D002470:Cell Survival / Q000187:drug effects; D004586:Electrophoresis / Q000379:methods; D006801:Humans; D018799:Intercellular Adhesion Molecule-1; D007375:Interleukin-1 / Q000502:physiology*; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000378:metabolism*; D009457:Neuroglia / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism; D014407:Tumor Cells, Cultured; D019010:Vascular Cell Adhesion Molecule-1
chemical_list: D000975:Antioxidants; D015815:Cell Adhesion Molecules; D007375:Interleukin-1; D016328:NF-kappa B; D017382:Reactive Oxygen Species; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1