Abstract
Prostaglandin E2 (PGE2) at concentrations more than 1×10−8 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 stand 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 effect on PHA-stimulated MNC as well as PGE2. These results suggest that the immunosupressive 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.
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Abbreviations
- PGE2 :
-
prostaglandin E2
- GSH:
-
glutathione
- MNC:
-
mononuclear cell
- PHA:
-
phytohemagglutinin
- sIL-2R:
-
soluble interleukin-2 receptor
- sCD4:
-
soluble CD4 molecule
- sCD8:
-
soluble CD8 molecule
- ELISa:
-
enzyme-linked immunosorbent assay
- BSO:
-
dl-buthionine-[S,R]-sulfoximine
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Yu, C.L., Liu, C.L., Tsai, C.Y. et al. Prostaglandin E2 suppresses phytohemagglutin-induced immune responses of normal human monoculear cells by decreasing intracellular glutathione generation, but not due to increased DNA strand breaks or apoptosis. Agents and Actions 40, 191–199 (1993). https://doi.org/10.1007/BF01984061
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DOI: https://doi.org/10.1007/BF01984061