Regulation of intercellular adhesion molecule-1 gene expression by tumor necrosis factor-alpha, interleukin-1 beta, and interferon-gamma in astrocytes.
Intercellular adhesion molecule-1 (ICAM-1) is a cell surface glycoprotein which can be induced on astrocytes, the major glial cell of the central nervous system (CNS). In this study, we examined the effect of three proinflammatory cytokines, tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta), and interferon-gamma (IFN-gamma), on the expression of ICAM-1 by primary rat astrocytes. Astrocytes constitutively express ICAM-1 mRNA and protein, which is enhanced by treatment with TNF-alpha, IL-1 beta and IFN-gamma. TNF-alpha is the most potent inducer of ICAM-1 expression, followed by IL-1 beta, then IFN-gamma. Kinetic analysis demonstrated optimum ICAM-1 mRNA expression after a 1-h exposure to TNF-alpha, 2 h exposure to IL-1 beta, and 4 h exposure to IFN-gamma. Peak ICAM-1 protein expression was detected 12-16 h after treatment with TNF-alpha or IL-1 beta, and after a 24-h exposure to IFN-gamma. Nuclear run-on analysis demonstrated that the ICAM-1 gene is transcribed under basal conditions in astrocytes, and that both TNF-alpha and IL-1 beta enhance transcriptional activation of the ICAM-1 gene. ICAM-1 mRNA stability studies determined that basal ICAM-1 mRNA has a half-life of about 1 h, and that TNF-alpha, IL-1 beta and IFN-gamma have a modest effect on stabilization of basal ICAM-1 mRNA expression. These results indicate that under inflammatory conditions in the CNS, such as multiple sclerosis (MS) and experimental allergic encephalomyelitis (EAE), astrocytes can be induced to express the adhesion molecule ICAM-1, which can contribute to inflammatory events within the CNS.
Shrikant
P
P
Department of Cell Biology, University of Alabama at Birmingham 35294.
Chung
I Y
IY
Ballestas
M E
ME
Benveniste
E N
EN
D000818:Animals; D001253:Astrocytes / Q000378:metabolism*; D001483:Base Sequence; D015815:Cell Adhesion Molecules / Q000235:genetics* / Q000502:physiology; D002478:Cells, Cultured; D003513:Cycloheximide / Q000494:pharmacology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000209:etiology; D005786:Gene Expression Regulation / Q000187:drug effects*; D018799:Intercellular Adhesion Molecule-1; D007371:Interferon-gamma / Q000494:pharmacology*; D007375:Interleukin-1 / Q000494:pharmacology*; D008969:Molecular Sequence Data; D051381:Rats; D014158:Transcription, Genetic / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D015815:Cell Adhesion Molecules; D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D007371:Interferon-gamma; D003513:Cycloheximide