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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
Author(s) -
HANSEN ALASTAIR B.,
BOUCHELOUCHE PIERRE N.,
GIESE BIRGITTE N.,
MØLLER PETER
Publication year - 1996
Publication title -
apmis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.909
H-Index - 88
eISSN - 1600-0463
pISSN - 0903-4641
DOI - 10.1111/j.1699-0463.1996.tb00719.x
Subject(s) - inositol , calcium , inositol phosphate , chemistry , phosphate , antigen , biophysics , biochemistry , endocrinology , medicine , immunology , biology , receptor , organic chemistry
In the present study, we investigated the effect of interferon‐gamma (IFN‐γ) on cellular inositol phosphate formation and cellular calcium ion concentration [Ca 2+ ] i in human renal proximal tubular (HRPT) cells. We also examined the possible role of the inositol phosphate‐Ca 2+ signalling pathway during IFN‐γ‐induced intercellular adhesion molecule‐1 (ICAM‐1) antigen expression. IFN‐γ caused an increase in the formation of inositol 1‐monophosphate (Ins 1‐P), inositol 1,4‐bisphosphate (Ins 1,4‐P 2 ), inositol 1,4,5‐trisphosphate (Ins 1,4,5‐P 3 ) and inositol 1,3,4,5‐tetrakisphosphate (Ins 1,3,4,5‐P 4 ). A rapid time‐dependent rise in [Ca 2+ ] i was observed upon IFN‐γ stimulation, with maximal levels reached after 1 min. A lower rise in [Ca 2+ ] i was observed when cells were stimulated in Ca 2+ ‐free medium. This correlated with the generation of Ins 1,4,5‐P 3 by IFN‐γ, a well‐known secondary messenger capable of releasing Ca 2+ from intracellular stores. The induction of ICAM‐1 antigen expression was enhanced by IFN‐γ, 4‐bromocalcium ionophore A23187 (Bromo‐A23187), and their combinations. However, the calcium antagonist diltiazem and calcium chelator EGTA had no effect on IFN‐γ antigen induction. In conclusion, our data suggest that IFN‐γ stimulation of HRPT cells results in the cleavage of phosphatidylinositol bisphosphate by phospholipase C, generating inositol phosphates, of which Ins 1,4,5‐P 3 probably releases Ca 2+ from intracellular stores. A further increase in [Ca 2+ ] i upon IFN‐γ stimulation results from influx of extracellular Ca 2+ . IFN‐γ signal transduction in HRPT cells may not be limited to the inositol phosphate‐Ca 2+ pathway since IFN‐γ‐induced ICAM‐1 antigen expression was unaffected by calcium antagonist/chelator.