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.
Trocmé
Candice
C
GREPI, Laboratoire d'Enzymologie, CHU Albert Michallon, BP 217, 38043 Grenoble Cedex 9, France. CTrocme@chu-grenoble.fr
Gaudin
Philippe
P
Berthier
Sylvie
S
Morel
Françoise
F
D001402:B-Lymphocytes / Q000187:drug effects / Q000378:metabolism* / Q000821:virology*; D002118:Calcium / Q000378:metabolism; D002461:Cell Line, Transformed; D002614:Chelating Agents / Q000494:pharmacology; D003208:Concanavalin A / Q000494:pharmacology; D004533:Egtazic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D015870:Gene Expression; D004854:Herpesvirus 4, Human / Q000472:pathogenicity*; D006801:Humans; D007700:Kinetics; D008070:Lipopolysaccharides / Q000494:pharmacology; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis / Q000235:genetics; D008985:Monensin / Q000494:pharmacology; D010641:Phenotype; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000096:biosynthesis* / Q000235:genetics
D002614:Chelating Agents; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D019715:Tissue Inhibitor of Metalloproteinase-1; D003208:Concanavalin A; C070379:1,2-bis(2-aminophenoxy)ethane N,N,N',N'-tetraacetic acid acetoxymethyl ester; D004533:Egtazic Acid; D008985:Monensin; D020780:Matrix Metalloproteinase 9; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium