       Document 0075
 DOCN  M9640075
 TI    IL-10 cooperates with TNF-alpha to activate HIV-1 from latently and
       acutely infected cells of monocyte/macrophage lineage.
 DT    9604
 AU    Finnegan A; Roebuck KA; Nakai BE; Gu DS; Rabbi MF; Song S; Landay AL;
       Department of Medicine, Rush-Presbyterian-St. Luke's Medical; Center,
       Chicago, IL 60612, USA.
 SO    J Immunol. 1996 Jan 15;156(2):841-51. Unique Identifier : AIDSLINE
       MED/96133016
 AB    IL-10 is elevated in HIV-1-infected individuals and has been implicated
       in disease progression. In this study, we investigated the effects of
       IL-10 on the activation of HIV-1 from infected monocytes and
       macrophages. Although IL-10 alone did not induce HIV-1 replication, in
       the presence of TNF-alpha, IL-10 markedly enhanced virion production
       from a chronically infected promonocytic cell line (U1) and in acutely
       infected monocyte-derived macrophages. Neutralizing mAbs to IL-10 and
       TNF-alpha indicated that both cytokines were essential for the induction
       and were required to generate a synergistic increase in virus
       expression. The effects of the two cytokines were distinguishable
       functionally since pretreatment with TNF-alpha attenuated the cytokine
       cooperativity, while pretreatment with IL-10 potentiated their
       cooperativity, suggesting that IL-10 and TNF-alpha play different roles
       in the activation of virus. Northern blot analysis as well as Ab
       blocking and cytokine secretion studies indicated that the induction of
       either endogenous TNF-alpha or IL-10 was not involved in the
       cooperativity, nor was an up-regulation of TNF-alpha receptors. In
       combination with TNF-alpha, IL-10 stimulated activating protein-1 (AP-1)
       and nuclear factor (NF)-kappa B binding activities and cooperated to
       increase HIV-1 steady-state mRNA levels and enhance long terminal
       repeat-directed transcription through activation of the NF-kappa B
       binding sites, suggesting the IL-10 effect occurs at least in part at
       the transcriptional level. These results indicate that IL-10, in
       addition to down-regulating the cellular immune response to HIV-1, may
       also play a role in TNF-alpha-mediated activation of HIV-1 replication
       in the monocyte/macrophage lineage.
 DE    Base Sequence  Drug Synergism  Gene Expression Regulation, Viral/*DRUG
       EFFECTS  Human  HIV Long Terminal Repeat  HIV-1/DRUG EFFECTS/*GROWTH &
       DEVELOPMENT  Interleukin-10/*PHARMACOLOGY  Lymphoma,
       Large-Cell/PATHOLOGY  Macrophages/*VIROLOGY  Molecular Sequence Data
       Monocytes/*VIROLOGY  NF-kappa B/METABOLISM  Recombinant Fusion
       Proteins/PHARMACOLOGY  RNA, Messenger/BIOSYNTHESIS  RNA,
       Viral/BIOSYNTHESIS  Support, Non-U.S. Gov't  Transcription Factor
       AP-1/METABOLISM  Transcription, Genetic/DRUG EFFECTS  Tumor Cells,
       Cultured  Tumor Necrosis Factor/*PHARMACOLOGY  Virus Activation/*DRUG
       EFFECTS  Virus Latency  Virus Replication  JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).

