Document 0022
 DOCN  M9480022
 TI    Prostaglandin E2 suppresses phytohemagglutinin-induced immune responses
       of normal human mononuclear cells by decreasing intracellular
       glutathione generation, but not due to increased DNA strand breaks or
       apoptosis.
 DT    9410
 AU    Yu CL; Liu CL; Tsai CY; Sun KH; Liao TS; Lin WM; Chen HL; Yu HS;
       Department of Medicine, Veterans General Hospital-Taipei, Taiwan,;
       Republic of China.
 SO    Agents Actions. 1993 Nov;40(3-4):191-9. Unique Identifier : AIDSLINE
       MED/94295468
 AB    Prostaglandin E2 (PGE2) at concentrations more than 1 x 10(-8) M
       markedly suppressed the cell proliferation and release of soluble
       molecules of interleukin-2 receptor (sIL-2R), CD4 (sCD4) and CD8 (sCD8)
       from phytohemagglutinin (PHA)-stimulated normal human mononuclear cells
       (MNC) in a dose-related manner. To further elucidate the subcellular
       mechanism of the inhibitory effect of PGE2 on PHA-stimulated MNC,
       intracellular concentration of glutathione (GSH) in PHA-stimulated MNC
       was sequentially measured from day 1 to day 3 by enzymic method.
       Furthermore, the effect of PGE2 on nuclear DNA including DNA strand
       breaks in alkali treatment and DNA fragmentation (apoptosis) of
       PHA-stimulated MNC were also measured. We found intracellular GSH levels
       were significantly decreased in the early stage of lymphocyte activation
       (day 1), but no evidence of increased DNA strand breaks or apoptotic
       process appeared in 3-day culture. In addition, butathione sulfoximine
       (a specific GSH inhibitor) and dibutyryl cyclic AMP also exhibited both
       proliferation inhibition and GSH-decreasing effects on PHA-stimulated
       MNC as well as PGE2. These results suggest that the immunosuppressive
       effect of PGE2 is mediated by the decreased generation of intracellular
       GSH, but not by the increased DNA strand breaks or apoptotic mechanism
       in the cells.
 DE    Antimetabolites/PHARMACOLOGY  Apoptosis/*DRUG EFFECTS
       Bucladesine/PHARMACOLOGY  Cell Cycle/DRUG EFFECTS  CD4-CD8 Ratio/DRUG
       EFFECTS  Dinoprostone/*PHARMACOLOGY  *DNA Damage  Enzyme-Linked
       Immunosorbent Assay  Glutathione/*BIOSYNTHESIS  Human  Immunity,
       Cellular/*DRUG EFFECTS  In Vitro  Lymphocyte Transformation/DRUG EFFECTS
       Methionine Sulfoximine/ANALOGS & DERIVATIVES/PHARMACOLOGY
       Monocytes/DRUG EFFECTS/*IMMUNOLOGY/METABOLISM
       Phytohemagglutinins/*ANTAGONISTS & INHIB/PHARMACOLOGY  Receptors,
       Interleukin-2/BIOSYNTHESIS  Support, Non-U.S. Gov't
       Thymidine/METABOLISM  JOURNAL ARTICLE

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