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Regulation of nucleoside transport regulation by lipopolysaccharide, phorbol esters and TNF in human B lymphocytes
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Nucleoside transport systems and their regulation in human B-lymphocytes have been characterized using the cell lines Raji and Bare lymphoma syndrome-1 (BLS-1) as experimental models. These cells express at least three different nucleoside transport systems as follows: a nitrobenzylthioinosine-sensitive equilibrative transport system of the es-type, which appears to be associated with hENT1 expression, and two Na+-dependent transport systems that may correspond to N1 and to the recently characterized N5-type, which is nitrobenzylthioinosine-sensitive and guanosine-preferring. B cell activators such as phorbol 12-myristate 13-acetate and lipopolysaccharide (LPS) up-regulate both concentrative transport systems but down-regulate the equilibrative es-type transporter, which correlates with lower hENT1 mRNA levels. These effects are dependent on protein kinase C activity. Phorbol 12-myristate 13-acetate and LPS also induce an increase in tumor necrosis factor-alpha (TNF-alpha) mRNA levels, which suggest that this cytokine may mediate some of the effects triggered by these agents, since addition of TNF-alpha alone can increase N1 and N5 transport activities by a mechanism that also depends on protein kinase C activation. Interestingly, TNF-alpha down-regulates es activity, but this effect cannot be abolished by inhibiting protein kinase C. This study reveals differential regulation of nucleoside transport systems following activation of human B-lymphocyte cell lines by agents of physiological relevance such as TNF-alpha and LPS. Moreover, it indicates that the recently characterized N5 transport system can also be regulated following B cell activation, which may be relevant to lymphocyte physiology and to the treatment of lymphocyte malignancies.
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SOLER PRAT, Concepció, FELIPE CAMPO, Antonio, MATA, João f., CASADO, Javier (casado merediz), CELADA COTARELO, Antonio, PASTOR ANGLADA, Marçal. Regulation of nucleoside transport regulation by lipopolysaccharide, phorbol esters and TNF in human B lymphocytes. _Journal of Biological Chemistry_. 1998. Vol. 273, núm. 41, pàgs. 26939-26945. [consulta: 21 de gener de 2026]. ISSN: 0021-9258. [Disponible a: https://hdl.handle.net/2445/177612]