Receptor-mediated down-regulation of neutral endopeptidase (NEP; EC 3.4.24.11; CD10) on immature B lymphocytes by dexamethasone

  • Authors:
    • Barbara Cupic
    • Davorka Breljak
    • Jelka Gabrilovac
  • View Affiliations

  • Published online on: June 1, 2005     https://doi.org/10.3892/ijmm.15.6.1023
  • Pages: 1023-1031
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Abstract

Neutral endopeptidase is a membrane bound enzyme with various functions depending on cell type or tissue origin. Normal development and differentiation of immature B lymphocytes depends on expression of CD10/NEP on B cell progenitors and bone marrow stromal cells. Synthetic glucocorticoid dexamethasone (dex), an immunosuppressive and anti-inflammatory drug, was shown to be a potent modulator of CD10/NEP expressed on cells of non-hematopoietic origin. We investigated the effect of dex on expression of differentiation marker CD10/NEP on immature B cells. The drug was applied in concentrations corresponding to the physiological range. CD10/NEP was measured at three levels of expression: mRNA (by means of duplex PCR), membrane protein marker (FACS analysis) and enzyme activity (hydrolysis of a selective chromogenic substrate). Dex down-regulated CD10/NEP expression on immature B cell line NALM-6 in a concentration- and time-dependent fashion. The effect was detected at all three levels. Dex-induced CD10/NEP down-regulation was mediated via glucocorticoid receptors (GR), as it was fully abrogated by a GR antagonist, RU 38486. That occurred at all three levels. The mechanism of dex-induced CD10/NEP down-regulation is not likely to include selection of cells that are CD10low since the effect was partly reversible after the removal of dex. However, dex-induced CD10/NEP down-regulation did include decreased transcription of the CD10 mRNA. Transcriptional inhibitor actinomycin D completely abolished dex-induced CD10/NEP down-regulation. Since differentiation of normal B lymphocytes is associated with down-regulation of CD10/NEP, the data presented suggest that low, physiologically relevant concentrations of glucocorticoids (such as observed in acute stress) may play a regulatory role in normal development and maturation of B lymphocytes.

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June 2005
Volume 15 Issue 6

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Spandidos Publications style
Cupic B, Breljak D and Gabrilovac J: Receptor-mediated down-regulation of neutral endopeptidase (NEP; EC 3.4.24.11; CD10) on immature B lymphocytes by dexamethasone. Int J Mol Med 15: 1023-1031, 2005.
APA
Cupic, B., Breljak, D., & Gabrilovac, J. (2005). Receptor-mediated down-regulation of neutral endopeptidase (NEP; EC 3.4.24.11; CD10) on immature B lymphocytes by dexamethasone. International Journal of Molecular Medicine, 15, 1023-1031. https://doi.org/10.3892/ijmm.15.6.1023
MLA
Cupic, B., Breljak, D., Gabrilovac, J."Receptor-mediated down-regulation of neutral endopeptidase (NEP; EC 3.4.24.11; CD10) on immature B lymphocytes by dexamethasone". International Journal of Molecular Medicine 15.6 (2005): 1023-1031.
Chicago
Cupic, B., Breljak, D., Gabrilovac, J."Receptor-mediated down-regulation of neutral endopeptidase (NEP; EC 3.4.24.11; CD10) on immature B lymphocytes by dexamethasone". International Journal of Molecular Medicine 15, no. 6 (2005): 1023-1031. https://doi.org/10.3892/ijmm.15.6.1023