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).