       Document 0541
 DOCN  M9610541
 TI    Induction of IL-6 and IL-10 production by recombinant HIV-1 envelope
       glycoprotein 41 (gp41) in the THP-1 human monocytic cell line.
 DT    9601
 AU    Takeshita S; Breen EC; Ivashchenko M; Nishanian PG; Kishimoto T;
       Vredevoe DL; Martinez-Maza O; UCLA School of Nursing, USA.
 SO    Cell Immunol. 1995 Oct 15;165(2):234-42. Unique Identifier : AIDSLINE
       MED/96021262
 AB    Elevated levels of circulating monokines (IL-6, IL-1, and TNF alpha)
       have been seen in HIV-1 infection, and the overproduction of these
       cytokines could contribute to AIDS pathogenesis in various ways. In
       previous work, we had seen that exposure of human monocytes to HIV-1,
       including inactivated, noninfectious HIV, led to rapid IL-6 gene
       expression and secretion. To investigate cytokine production in response
       to components of HIV by monocytes/macrophages, production of IL-6 and
       IL-10 were examined in a human monocytic cell line, THP-1, stimulated by
       HIV proteins. IL-6 production was induced in THP-1 cells by a detergent
       lysate of HIV, particularly fractions at molecular weight of 25-50 kDa.
       Recombinant HIV envelope glycoprotein 41 (gp41), but not gp120 or p24,
       also was seen to induce significant IL-6 production by THP-1 cells.
       These results suggest that gp41, transmembrane protein, is the primary
       HIV-encoded protein involved in inducing IL-6 production. IL-10 was also
       produced with delayed kinetics, following IL-6 production in THP-1 cells
       stimulated by gp41. To investigate a possible regulatory role for IL-10
       in HIV-induced monokine production, recombinant IL-10 was added to
       gp41-exposed THP-1 cells. IL-10 inhibited gp41-induced IL-6 production
       and reduced the expression of IL-6 mRNA. When anti-human IL-10
       neutralizing antibody was added to THP-1 cells, IL-6 production was
       enhanced. These results suggest that the IL-6 production may be
       downregulated by endogenously produced IL-10 and that IL-10 may
       downregulate cytokine production by HIV-activated monocytes via an
       autoregulatory mechanism.
 DE    Base Sequence  Cell Line  Human  HIV Core Protein p24/PHARMACOLOGY  HIV
       Envelope Protein gp120/PHARMACOLOGY  HIV Envelope Protein
       gp41/*PHARMACOLOGY  HIV-1/*PHYSIOLOGY
       Interleukin-10/*BIOSYNTHESIS/GENETICS/PHARMACOLOGY
       Interleukin-6/*BIOSYNTHESIS  Molecular Sequence Data
       Monocytes/*METABOLISM  Recombinant Proteins/PHARMACOLOGY  RNA,
       Messenger/ANALYSIS  Support, U.S. Gov't, P.H.S.  JOURNAL ARTICLE

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

