Abstract |
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.
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Authors | G Denecker, P Vandenabeele, J Grooten, L C Penning, W Declercq, R Beyaert, W A Buurman, W Fiers |
Journal | Cytokine
(Cytokine)
Vol. 9
Issue 9
Pg. 631-8
(Sep 1997)
ISSN: 1043-4666 [Print] England |
PMID | 9325011
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Chlorides
- Interleukin-1
- Tumor Necrosis Factor-alpha
- Zinc Compounds
- Aurintricarboxylic Acid
- Egtazic Acid
- Granulocyte-Macrophage Colony-Stimulating Factor
- Cyclosporine
- zinc chloride
- Calcineurin
- 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid
- Calcium
- Tacrolimus
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Topics |
- Animals
- Apoptosis
- Aurintricarboxylic Acid
(pharmacology)
- Calcineurin
(physiology)
- Calcium
(physiology)
- Chlorides
(pharmacology)
- Cyclosporine
(pharmacology)
- Dose-Response Relationship, Drug
- Egtazic Acid
(analogs & derivatives, pharmacology)
- Granulocyte-Macrophage Colony-Stimulating Factor
(metabolism)
- Hybridomas
(metabolism)
- Interleukin-1
(pharmacology)
- Mice
- Rats
- T-Lymphocytes
(metabolism)
- Tacrolimus
(pharmacology)
- Time Factors
- Tumor Necrosis Factor-alpha
(pharmacology)
- Zinc Compounds
(pharmacology)
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