TY - JOUR
T1 - Regulation of intercellular adhesion molecule-1 gene expression by tumor necrosis factor-α, interleukin-1β, and interferon-γ in astrocytes
AU - Shrikant, Protul
AU - Il Yup Chung, Yup Chung
AU - Ballestas, Mary E.
AU - Benveniste, Etty N.
N1 - Funding Information:
We thank Sue Wade for excellent secretarial and editorial assistance. Supported in part by Grants 2269-A4 and 2205-B5 from the National Multiple Sclerosis Society (E.N.B.) and National Institutes of Health Grant NS-29719 (E.N.B.). M.E.B, is the recipient of a Patricia Roberts Harris Fellowship.
PY - 1994/5
Y1 - 1994/5
N2 - 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-α), interleukin-1 beta (IL-1β), and interferon-gamma (IFN-γ), 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-α, IL-1β and IFN-γ. TNF-α is the most potent inducer of ICAM-1 expression, followed by IL-1β, then IFN-γ. Kinetic analysis demonstrated optimum ICAM-1 mRNA expression after a 1-h exposure to TNF-α, 2 h exposure to IL-1β, and 4 h exposure to IFN-γ. Peak ICAM-1 protein expression was detected 12-16 h after treatment with TNF-α or IL-1β, and after a 24-h exposure to IFN-γ. Nuclear run-on analysis demonstrated that the ICAM-1 gene is transcribed under basal conditions in astrocytes, and that both TNF-α and IL-1β 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-α, IL-1β and IFN-γ 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.
AB - 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-α), interleukin-1 beta (IL-1β), and interferon-gamma (IFN-γ), 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-α, IL-1β and IFN-γ. TNF-α is the most potent inducer of ICAM-1 expression, followed by IL-1β, then IFN-γ. Kinetic analysis demonstrated optimum ICAM-1 mRNA expression after a 1-h exposure to TNF-α, 2 h exposure to IL-1β, and 4 h exposure to IFN-γ. Peak ICAM-1 protein expression was detected 12-16 h after treatment with TNF-α or IL-1β, and after a 24-h exposure to IFN-γ. Nuclear run-on analysis demonstrated that the ICAM-1 gene is transcribed under basal conditions in astrocytes, and that both TNF-α and IL-1β 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-α, IL-1β and IFN-γ 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.
KW - Adhesion molecules
KW - Central nervous system
KW - Cytokines
KW - Glial cells
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U2 - 10.1016/0165-5728(94)90083-3
DO - 10.1016/0165-5728(94)90083-3
M3 - Article
C2 - 7910170
AN - SCOPUS:0028351424
SN - 0165-5728
VL - 51
SP - 209
EP - 220
JO - Journal of neuroimmunology
JF - Journal of neuroimmunology
IS - 2
ER -