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Interferon-gamma increases inositol phosphate formation and cellular calcium ion concentration independent of ICAM-1 antigen enhancement in renal tubular cells.
- Source :
-
APMIS : acta pathologica, microbiologica, et immunologica Scandinavica [APMIS] 1996 Apr; Vol. 104 (4), pp. 285-92. - Publication Year :
- 1996
-
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.
- Subjects :
- Calcimycin analogs & derivatives
Calcimycin pharmacology
Calcium antagonists & inhibitors
Cells, Cultured
Humans
Intercellular Adhesion Molecule-1 biosynthesis
Intercellular Adhesion Molecule-1 drug effects
Intracellular Fluid drug effects
Intracellular Fluid metabolism
Ionophores pharmacology
Kidney Tubules, Proximal cytology
Calcium metabolism
Inositol Phosphates biosynthesis
Intercellular Adhesion Molecule-1 immunology
Interferon-gamma pharmacology
Kidney Tubules, Proximal drug effects
Kidney Tubules, Proximal immunology
Subjects
Details
- Language :
- English
- ISSN :
- 0903-4641
- Volume :
- 104
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- APMIS : acta pathologica, microbiologica, et immunologica Scandinavica
- Publication Type :
- Academic Journal
- Accession number :
- 8645468
- Full Text :
- https://doi.org/10.1111/j.1699-0463.1996.tb00719.x