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1996-03-09
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Document 0427
DOCN M9650427
TI HIV glycoprotein 120 enhances intercellular adhesion molecule-1 gene
expression in glial cells. Involvement of Janus kinase/signal transducer
and activator of transcription and protein kinase C signaling pathways.
DT 9605
AU Shrikant P; Benos DJ; Tang LP; Benveniste EN; Department of Cell
Biology, University of Alabama, Birmingham; 35294, USA.
SO J Immunol. 1996 Feb 1;156(3):1307-14. Unique Identifier : AIDSLINE
MED/96144358
AB It is well established that the two major glial cells in the central
nervous system (CNS), astrocytes and microglia, are key participants in
mediating the neurologic dysfunction associated with HIV infection of
the CNS. In this study, we investigated the ability of the major
envelope glycoprotein of HIV, glycoprotein 120 (gp120), to regulate
intercellular adhesion molecule-1 (ICAM-1) expression in glial cells,
because ICAM-1 is important in mediating immune responsiveness in the
CNS, facilitating entry of HIV-infected cells into the CNS, and
promoting syncytia formation. Our results indicate that gp120 enhances
ICAM-1 gene expression in primary rat astrocytes, primary human
astrocytes, a human astroglioma cell line CRT, and primary rat
microglia. The signal transduction events involved in gp120-mediated
enhancement of ICAM-1 appear to involve activation of both protein
kinase C and tyrosine kinase, because inhibitors of protein kinase C and
tyrosine kinase abrogate gp120-mediated ICAM-1 expression in both
astrocytes and microglia. Moreover, gp120 induces tyrosine
phosphorylation of signal transducer and activator of transcription
(STAT-1 alpha) as well as the Janus kinase (JAK2) in glial cells. We
also demonstrate that gp120-mediated ICAM-1 expression has functional
significance, as it enhances the ability of monocytic cells to bind to
gp120-stimulated human astrocytes in an ICAM-1/beta 2 integrin-dependent
fashion. These results provide new insights into how gp120 can influence
the involvement of glial cells in the pathogenesis of AIDS dementia
complex.
DE Animal Antigens, CD18/METABOLISM Astrocytes/METABOLISM
Astrocytoma/IMMUNOLOGY/PATHOLOGY Cell Adhesion Cell Line DNA-Binding
Proteins/PHYSIOLOGY Human HIV Envelope Protein gp120/*PHYSIOLOGY
HIV-1/*PHYSIOLOGY Intercellular Adhesion
Molecule-1/*BIOSYNTHESIS/GENETICS Macrophage Activation
Microglia/METABOLISM Monocytes/METABOLISM Neuroglia/*DRUG
EFFECTS/METABOLISM Phosphorylation Protein Kinase C/*PHYSIOLOGY
Protein-Tyrosine Kinase/*PHYSIOLOGY Rats RNA, Messenger/ANALYSIS
Signal Transduction/*PHYSIOLOGY Support, U.S. Gov't, P.H.S.
Trans-Activators/PHARMACOLOGY/PHYSIOLOGY Tumor Cells, Cultured JOURNAL
ARTICLE
SOURCE: National Library of Medicine. NOTICE: This material may be
protected by Copyright Law (Title 17, U.S.Code).