title: Interferon-gamma increases cellular calcium ion concentration and inositol 1,4,5-trisphosphate formation in human renal carcinoma cells: relation to ICAM-1 antigen expression.
abstract: In the present study, we investigated the effect of interferon-gamma (IFN-gamma) on cellular calcium ion concentration [Ca2+]i and inositol 1,4,5-trisphosphate (Ins 1,4,5-P3) formation in the human renal carcinoma cell line CaKi-1. We also examined the possible role of a Ca(2+)-dependent mechanism during IFN-gamma-induced intercellular adhesion molecule 1 (ICAM-1) antigen expression. IFN-gamma caused a rapid concentration-dependent rise in [Ca2+]i, which was partly inhibited by diltiazem, a calcium channel blocker, TMB-8, an inhibitor of intracellular calcium redistribution, and in calcium-free medium. IFN-gamma caused a fourfold increase in Ins 1,4,5-P3 formation. The induction of ICAM-1 antigen expression was synergistically enhanced by 4-bromocalcium ionophore A23187. Finally, the calcium antagonists diltiazem. TMB-8 and EGTA, as well as two potent inhibitors of Ca(2+)-dependent kinases, calmidazolium (R24571) and W7, had no or only a minor inhibitory effect on IFN-gamma induction. Our data suggest that IFN-gamma increases [Ca2+]i in CaKi-1 cells by stimulating influx of Ca2+ and release of Ca2+ from intracellular stores, probably via Ins 1,4,5-P3 formation. IFN-gamma signal transduction in our model may not be limited to an increase in [Ca2+]i and Ins 1,4,5-P3, since IFN-gamma-induced ICAM-1 antigen expression was abrogated to a minor degree by calcium antagonists and not coupled to Ins 1,4,5-P3 formation.
authors.affiliation: Department of Pathology, Herlev Hospital, University of Copenhagen, Denmark.
authors.forename: A B
authors.initials: AB
authors.lastname: Hansen
authors.forename: P N
authors.initials: PN
authors.lastname: Bouchelouche
authors.forename: S T
authors.initials: ST
authors.lastname: Lillevang
authors.forename: C B
authors.initials: CB
authors.lastname: Andersen
mesh_terms: D000941:Antigens / Q000378:metabolism*; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000037:antagonists & inhibitors / Q000378:metabolism*; D002292:Carcinoma, Renal Cell / Q000378:metabolism*; D015815:Cell Adhesion Molecules / Q000276:immunology*; D002470:Cell Survival / Q000187:drug effects; D003470:Culture Media; D054746:Cyclic AMP-Dependent Protein Kinase Type II; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D015544:Inositol 1,4,5-Trisphosphate / Q000096:biosynthesis*; D018799:Intercellular Adhesion Molecule-1; D007371:Interferon-gamma / Q000494:pharmacology*; D007680:Kidney Neoplasms / Q000378:metabolism*; D013449:Sulfonamides / Q000494:pharmacology; D014407:Tumor Cells, Cultured
chemical_list: D000941:Antigens; D015815:Cell Adhesion Molecules; D003470:Culture Media; D007093:Imidazoles; D013449:Sulfonamides; D018799:Intercellular Adhesion Molecule-1; D000001:Calcimycin; C031938:calmidazolium; C017967:W 7; D007371:Interferon-gamma; D015544:Inositol 1,4,5-Trisphosphate; D054746:Cyclic AMP-Dependent Protein Kinase Type II; D017868:Cyclic AMP-Dependent Protein Kinases; D002118:Calcium