engleski

Regulation of CD10/NEP on immature B-cell line by dexamethasone and IL-4

Neutral endopeptidase (NEP ; EC 3.4.24.11 ; CD10 ; CALLA ; enkephalinase) is a broadly distributed membrane-bound metallopeptidase. Its function varies from cell and tissue type on which it is expressed. Due to enzymatic activity (cleavage of peptides on the amino side of hydrophobic amino acids) NEP regulates local concentrations of various signaling peptides, taking part in fundamental physiological processes: growth, differentiation and activation. Among the cells of hematopoietic origin CD10 is expressed on early lymphoid precursors and differentiation of both T and B lymphocytes is influenced by CD10 expressed on stromal cells (Guerin et al., FASEB J., 11:376-381, 1997). Re-expression of CD10 on mature, resting B lymphocytes was reported (Ingvarsson et al., Int. Immunol., 11:739-744, 1999). CD10 is highly expressed on mature granulocytes where it plays important role in regulation of inflammatory response. Anti-inflammatory and immuno-suppressive drug dexamethasone, was reported to up-regulate CD10/NEP on bronchial epithelial cells (van der Velden et al., Cytokine, 10:55-65, 1998). In this study we examined the ability of dexamethasone and cytokine IL-4 to regulate CD10/NEP on cells of immature B-cell line, NALM-6. That was done by measuring mRNA for CD10 (duplex RT-PCR), CD10 membrane expression (FACS analysis), and NEP enzyme activity (hydrolysis of fluorochrome-labeled substrate). NALM-6 cells were exposed to dexamethasone (50, 10, 5 nM) or IL-4 (100, 50, 25, 12.5 U/mL) for 1, 2, 3 and 4 days. The data obtained have shown that dexamethasone down-regulated CD10/NEP in a dose- and time-dependent manner at all three levels. The effects of dexamethasone were reversible as CD10 expression (mRNA and membrane protein) partly recovered 3 days after discontinuation of the treatment. In contrast to dexamethasone, IL-4 only mildly and transiently increased CD10 expression. Thus, strong but reversible down-regulation of CD10/NEP by dexamethasone, and mild, transient up-regulation of CD10 by IL-4 were found on immature B-cell line NALM-6. These data may help better understanding of the role of CD10/NEP and its regulation on early lymphoid precursors.

neutral endopeptidase; NEP; CD10; dexamethasone; IL-4; B-lymphocytes; regulation

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