Regulation of TIMP-1 phenotypic expression in Epstein--Barr virus-immortalized B lymphocytes

Normal B lymphocytes as well as malignant B cells extravasate from blood circulation during physiological and pathological processes and require matrix metalloproteinases (MMPs) to facilitate trafficking through the subendothelial basal lamina and the extracellular matrix. We have previously shown that Epstein-Barr virus (EBV)-immortalized B lymphocytes constitutively synthesized low levels of MMP-9 and huge amounts of its preferential inhibitor, tissue inhibitor of matrix metalloproteinase-1 (TIMP-1). In the present study, TIMP-1 phenotypic expression was extensively investigated in response to various mediators including interleukins, chemokines, growth factors and tumor promotor, and was compared to MMP-9 synthesis. Results showed a roughly constitutive TIMP-1 expression opposed to an inducible MMP-9 synthesis. Nevertheless, further analysis of TIMP-1 synthesis showed the existence of regulation mechanisms: modulation of intracellular Ca(2+) concentration as well as cation ionophore monensin were demonstrated to influence TIMP-1 production and secretion. The precise pathways implicated in these regulation mechanisms are currently under survey.