title: Interferon-gamma increases inositol phosphate formation and cellular calcium ion concentration independent of ICAM-1 antigen enhancement in renal tubular cells.
abstract: In the present study, we investigated the effect of interferon-gamma (IFN-gamma) on cellular inositol phosphate formation and cellular calcium ion concentration [Ca2+]i in human renal proximal tubular (HRPT) cells. We also examined the possible role of the inositol phosphate-Ca2+ signalling pathway during IFN-gamma-induced intercellular adhesion molecule-1 (ICAM-1) antigen expression. IFN-gamma caused an increase in the formation of inositol 1-monophosphate (Ins 1-P), inositol 1,4-bisphosphate (Ins 1,4-P2), inositol 1,4,5-trisphosphate (Ins 1,4,5-P3) and inositol 1,3,4,5-tetrakisphosphate (Ins 1,3,4,5-P4). A rapid time-dependent rise in [Ca2+]i was observed upon IFN-gamma stimulation, with maximal levels reached after 1 min. A lower rise in [Ca2+]i was observed when cells were stimulated in Ca2+-free medium. This correlated with the generation of Ins 1,4,5-P3 by IFN-gamma, a well-known secondary messenger capable of releasing Ca2+ from intracellular stores. The induction of ICAM-1 antigen expression was enhanced by IFN-gamma, 4-bromocalcium ionophore A23187 (Bromo-A23187), and their combinations. However, the calcium antagonist diltiazem and calcium chelator EGTA had no effect on IFN-gamma antigen induction. In conclusion, our data suggest that IFN-gamma stimulation of HRPT cells results in the cleavage of phosphatidylinositol bisphosphate by phospholipase C, generating inositol phosphates, of which Ins 1,4,5-P3 probably releases Ca2+ from intracellular stores. A further increase in [Ca2+]i upon IFN-gamma stimulation results from influx of extracellular Ca2+. IFN-gamma signal transduction in HRPT cells may not be limited to the inositol phosphate-Ca2+ pathway since IFN-gamma-induced ICAM-1 antigen expression was unaffected by calcium antagonist/chelator.
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: B N
authors.initials: BN
authors.lastname: Giese
authors.forename: P
authors.initials: P
authors.lastname: Møller
mesh_terms: D000001:Calcimycin / Q000031:analogs & derivatives / Q000494:pharmacology; D002118:Calcium / Q000037:antagonists & inhibitors / Q000378:metabolism*; D002478:Cells, Cultured; D006801:Humans; D007295:Inositol Phosphates / Q000096:biosynthesis*; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis / Q000187:drug effects / Q000276:immunology*; D007371:Interferon-gamma / Q000494:pharmacology*; D007424:Intracellular Fluid / Q000187:drug effects / Q000378:metabolism; D007476:Ionophores / Q000494:pharmacology; D007687:Kidney Tubules, Proximal / Q000166:cytology / Q000187:drug effects* / Q000276:immunology*
chemical_list: D007295:Inositol Phosphates; D007476:Ionophores; D018799:Intercellular Adhesion Molecule-1; D000001:Calcimycin; C033170:4-bromo-A-23187; D007371:Interferon-gamma; D002118:Calcium