       Document 0339
 DOCN  M9630339
 TI    Regulation of the balance of cytokine production and the signal
       transducer and activator of transcription (STAT) transcription factor
       activity by cytokines and inflammatory synovial fluids.
 DT    9603
 AU    Wang F; Sengupta TK; Zhong Z; Ivashkiv LB; Department of Medicine,
       Hospital for Special Surgery, New York,; USA.
 SO    J Exp Med. 1995 Dec 1;182(6):1825-31. Unique Identifier : AIDSLINE
       MED/96096457
 AB    The balance between type 1 and 2 T helper cell cytokine production plays
       an important role in several animal models of autoimmunity, and skewed
       patterns of cytokine expression have been described in human
       inflammatory diseases. Many cytokines activate signal transducer and
       activation of transcription (STAT) transcription factors, which, in
       turn, activate transcription of inflammatory effector genes. We used
       mononuclear cell priming cultures and inflammatory synovial fluids (SFs)
       derived from arthritis patients to examine the regulation of cytokine
       production and STAT activity by an inflammatory synovial
       microenvironment. Exposure to SFs during priming resulted in an 81%
       inhibition of interferon (IFN)-gamma, but not interleukin (IL) 4,
       production by effector cells generated in priming cultures. SF
       suppression was mediated by IL-4 and IL-10 and inhibition of IL-12
       expression, and it was reversed in a dominant fashion by exogenous
       IL-12. SFs blocked the sustained activity of transcription factor Stat1,
       but not Stat3, during the priming period, and Stat1 activity was
       differentially regulated by cytokines in parallel with their positive or
       negative regulation of IFN-gamma production. Active Stat3, but not
       Stat1, was detected in cells from inflamed joints. These results suggest
       a role for altered balance of Stat1 and Stat3 transcriptional activity
       in the regulation of T cell differentiation and in the pathogenesis of
       inflammatory synovitis.
 DE    Arthritis, Rheumatoid/*IMMUNOLOGY  Base Sequence  Cells, Cultured
       Cytokines/GENETICS/*METABOLISM  DNA Primers/CHEMISTRY  DNA-Binding
       Proteins/*PHYSIOLOGY  Gene Expression  Human  Interferon Type
       II/GENETICS/*METABOLISM  Interleukins/PHYSIOLOGY  Molecular Sequence
       Data  RNA, Messenger/GENETICS  Support, Non-U.S. Gov't  Support, U.S.
       Gov't, P.H.S.  Synovial Fluid/*IMMUNOLOGY  Synovitis/IMMUNOLOGY  Th2
       Cells/IMMUNOLOGY  Trans-Activators/*PHYSIOLOGY  JOURNAL ARTICLE

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

