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

Autori
Čupić, Barbara ; Breljak, Davorka ; Gabrilovac, Jelka

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
Book of Abstracts of the 1st International Alfried Krupp Kolleg-Symposium on Stress, behaviour, immune response / Richert, Maja - Greifswald, 2004, 14-15

Skup
1st International Alfried Krupp Kolleg-Symposium on Stress, behaviour, immune response

Mjesto i datum
Greifswald, Njemačka, 11.11.2004. - 13.11.2004

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
neutral endopeptidase; NEP; CD10; dexamethasone; B-lymphocytes; regulation; stress

Sažetak
Neutral endopeptidase is a membrane bound enzyme with various functions depending on cell type or tissue origin. Normal development and differentiation of immature B cells 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 NEP/CD10 expressed on cells of nonhematopoietic origin. In this study, we investigated the effect of dexamethasone 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 followed at three levels: mRNA (duplex PCR), membrane marker expression (FACS analysis) and enzyme activity (hydolysis of a selective chromogenic substrate). Dexamethasone down-regulated CD10/NEP expression on immature B cell line NALM-6, in a concentration- and time-dependent fashion. The effect was detected at the mRNA and protein levels, as well as at the level of the functional (enzyme) activity. Dex-induced CD10/NEP down-regulation was mediated via glucocorticoid receptors (GR), as it was fully abrogated by a GR antagonist, RU 38486 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 reversed 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 glucocorticoid reported in acute stress, may play regulatory role in normal development and maturation of B lymphocytes.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti

POVEZANOST RADA