Effect of verapamil on the class I major histocompatibility complex antigen expression in K562 chronic myelogenous leukemia cells treated with recombinant human interferon-gamma.
The effects of various compounds which modulated the intracellular signal transduction on the induction of class I major histocompatibility complex (MHC) antigens by recombinant human interferon-gamma (rIFN-gamma) were investigated using K562, chronic myelogenous leukemia cells. Class I or class II MHC antigens were not expressed in untreated K562 cells and rIFN-gamma (600 units/ml) weakly induced class I antigens on the cells. Among the compounds tested, verapamil but not the calcium ionophore A23187 enhanced the rIFN-gamma-induced class I antigen expression at both the surface molecule and mRNA levels and enhancement by verapamil occurred in a dose-dependent manner at non-toxic concentrations examined (approximately 50 microM). Verapamil alone had no inducible effect on MHC antigen expression. Deprivation of Ca2+ in culture medium by ethylene glycol-bis(beta-aminoethyl ether) N,N,N',N'-tetraacetic acid (EGTA) could not cause an enhancement of class I antigen induction by rIFN-gamma. Simultaneous exposure of K562 cells to rIFN-gamma (600 units/ml) and recombinant human tumor necrosis factor (rTNF; 1000 units/ml) in combination with verapamil (50 microM) resulted in a further increase of class I antigens in the cells. The expressions of c-myc oncogene in K562 cells were not changed when the cells were treated with rIFN-gamma (600 units/ml) or verapamil (50 microM), either alone or in combination. These results indicate that verapamil synergistically interacts with rIFN-gamma on the class I antigen induction in K562 cells irrespective of c-myc gene expression and that class I antigen induction in this cell line may not be relevant to calcium influx triggered by IFN-gamma.
Takemura
Y
Y
Department of Laboratory Medicine, National Defense Medical College, Saitama, Japan.
Koide
Y
Y
Miyachi
H
H
Shibata
T
T
Sekiguchi
S
S
Tukemura
Y
Y
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D000911:Antibodies, Monoclonal; D015152:Blotting, Northern; D000001:Calcimycin / Q000494:pharmacology; D002147:Calmodulin / Q000037:antagonists & inhibitors; D002460:Cell Line; D004533:Egtazic Acid / Q000494:pharmacology; D005805:Genes, MHC Class I / Q000187:drug effects*; D016259:Genes, myc / Q000187:drug effects; D015395:Histocompatibility Antigens Class I / Q000032:analysis / Q000096:biosynthesis*; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D007546:Isoquinolines / Q000494:pharmacology; D007700:Kinetics; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive; D010879:Piperazines / Q000494:pharmacology; D047428:Protein Kinase Inhibitors; D012334:RNA, Neoplasm / Q000032:analysis; D011994:Recombinant Proteins / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D013449:Sulfonamides / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D014700:Verapamil / Q000494:pharmacology*
D000911:Antibodies, Monoclonal; D002147:Calmodulin; D015395:Histocompatibility Antigens Class I; D007546:Isoquinolines; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D012334:RNA, Neoplasm; D011994:Recombinant Proteins; D013449:Sulfonamides; D014409:Tumor Necrosis Factor-alpha; D000001:Calcimycin; D004533:Egtazic Acid; C017967:W 7; D007371:Interferon-gamma; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D014700:Verapamil