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Modulation of P2X7 nucleotide receptor expression by pro- and anti-inflammatory stimuli in THP-1 monocytes.
- Source :
-
Journal of leukocyte biology [J Leukoc Biol] 1998 Aug; Vol. 64 (2), pp. 265-73. - Publication Year :
- 1998
-
Abstract
- Regulation of P2X7 receptor expression is of interest because activation of this receptor by extracellular ATP triggers maturation and release of the pro-inflammatory cytokine interleukin-1 beta (IL-1 beta) in monocytes and macrophages. We report that interferon-gamma (IFN-gamma) and tumor necrosis factor alpha (TNF-alpha) synergistically induce P2X7R mRNA and functional responses in the human THP-1 monocytic cell line. Induction was dose dependent, with maximal functional activity requiring 1000 units/mL IFN-gamma and 10 ng/mL TNF-alpha and incubations of 36-72 h. The up-regulation of P2X7R function by lipopolysaccharide (LPS)/IFN-gamma and TNF-alpha/IFN-gamma was markedly attenuated by coincubation with prostaglandin E2 or the cell permeant cyclic AMP analog dibutryl cAMP (Bt2cAMP). Bt2cAMP did not significantly alter P2X7 function in HEK-293 cells stably transfected with the human P2X7 cDNA, indicating that Bt2cAMP does not exert a generalized effect on P2X7R synthesis or downstream signal transduction. These studies demonstrate that elevated cAMP negatively modulates P2X7R expression.
- Subjects :
- Adenosine Triphosphate analogs & derivatives
Adenosine Triphosphate pharmacology
Affinity Labels pharmacology
Bucladesine pharmacology
Carcinogens pharmacology
Cell Differentiation drug effects
Cyclic AMP metabolism
Drug Synergism
Gene Expression drug effects
Gene Expression immunology
Humans
Interleukin-1 metabolism
Macrophages cytology
Macrophages drug effects
Macrophages immunology
Monocytes cytology
Monocytes drug effects
RNA, Messenger analysis
Receptors, Purinergic P2 immunology
Receptors, Purinergic P2X7
Second Messenger Systems immunology
Tetradecanoylphorbol Acetate pharmacology
Transfection
Tumor Cells, Cultured cytology
Tumor Cells, Cultured drug effects
Tumor Cells, Cultured immunology
Interferon-gamma pharmacology
Monocytes immunology
Receptors, Purinergic P2 genetics
Tumor Necrosis Factor-alpha pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 0741-5400
- Volume :
- 64
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Journal of leukocyte biology
- Publication Type :
- Academic Journal
- Accession number :
- 9715267
- Full Text :
- https://doi.org/10.1002/jlb.64.2.265