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M9480022.TXT
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1994-08-09
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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).