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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

  • Molecular Immunopathology
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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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Authors and Affiliations

  1. School of Medical Technology, National Yang-Ming Medical College, #201 Section 2, Shih-Pai Road, 11217, Taipei, Taiwan Republic of China

    K. -H. Sun

  2. Department of Dermatology, Kaohsiung Medical College, #100 Shih-Chuan 1st Road, 80708, Kaohsiung, Taiwan, Republic of China

    H. -S. Yu

  3. Section of Allergy, I Immunology and Rheumatolggym, Department of Medicine, Veterans General Hospital-Taipei, National Yang-Ming Medical College, #201 Section 2, Shh-Pai Road, 11217, Taipei, Taiwan, Republic of China

    C. -L. Yu, C. -L. Liu, C. -Y. Tsai, T. -S. Liao, W. -M. Lin & H. -L. Chen

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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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