Differential role of calcium in tumour necrosis factor-mediated apoptosis and secretion of granulocyte-macrophage colony-stimulating factor in a T cell hybridoma.

G. Denecker, P. Vandenabeele, J. Grooten, L.C. Penning, W. Declercq, R. Beyaert, W.A. Buurman, W. Fiers

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Abstract

Laboratory of Molecular Biology, Flanders Interuniversity Institute for Biotechnology, Ghent, Belgium.

The authors investigated the dependence on extracellular and intracellular free Ca2+ in the induction of apoptosis and secretion of granulocyte-macrophage colony-stimulating factor (GM-CSF) by tumour necrosis factor (TNF) in a rat/mouse T cell hybridoma PC60 R55/R75, using the Ca2+ chelators EGTA and BAPTA/AM, respectively. TNF-induced apoptosis still occurred in the absence of free Ca2+, while GM-CSF production required the continuous presence of Ca2+. The latter was also true for GM-CSF production driven by interleukin 1 (IL-1). The dependence on Ca2+ in the induction of GM-CSF, but not of apoptosis, was further confirmed by the inhibition of TNF- or IL-1-induced cytokine production by cyclosporin A or FK506, drugs that block the Ca2+/calmodulin-dependent protein Ser/Thr phosphatase calcineurin. This differential requirement for Ca2+ illustrates the partial functional redundancy between TNF and IL-1, showing the activation of cytokine gene expression through a Ca(2+)-dependent activation of calcineurin, and a Ca(2+)-independent activation of apoptosis, exerted solely by TNF.
Original languageEnglish
Pages (from-to)631-638
Number of pages8
JournalCytokine
Volume9
Issue number9
DOIs
Publication statusPublished - 1 Jan 1997

Cite this

Denecker, G., Vandenabeele, P., Grooten, J., Penning, L. C., Declercq, W., Beyaert, R., Buurman, W. A., & Fiers, W. (1997). Differential role of calcium in tumour necrosis factor-mediated apoptosis and secretion of granulocyte-macrophage colony-stimulating factor in a T cell hybridoma. Cytokine, 9(9), 631-638. https://doi.org/10.1006/cyto.1997.0218