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Modulation of P2X 7 nucleotide receptor expression by pro‐ and anti‐inflammatory stimuli in THP‐1 monocytes
Author(s) -
Humphreys Benjamin D.,
Dubyak George R.
Publication year - 1998
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1002/jlb.64.2.265
Subject(s) - biology , lipopolysaccharide , receptor , signal transduction , thp1 cell line , cytokine , tumor necrosis factor alpha , extracellular , monocyte , microbiology and biotechnology , intracellular , cell culture , interleukin 10 , transfection , endocrinology , medicine , immunology , biochemistry , genetics
Regulation of P2X7 receptor expression is of interest because activation of this receptor by extracellular ATP triggers maturation and release of the proinflammatory cytokine interleukin‐1β (IL‐1β) in monocytes and macrophages. We report that interferon‐γ (IFN‐γ) and tumor necrosis factor α (TNF‐α) synergistically induce P2X 7 R 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‐γ and 10 ng/mL TNF‐α and incubations of 36–72 h. The up‐regulation of P2X 7 R function by lipopolysaccharide (LPS)/IFN‐γ and TNF‐α/IFN‐γ was markedly attenuated by coincubation with prostaglandin E 2 or the cell permeant cyclic AMP analog dibutyryl cAMP (Bt 2 cAMP). Bt 2 cAMP did not significantly alter P2X 7 function in HEK‐293 cells stably transfected with the human P2X 7 cDNA, indicating that Bt 2 cAMP does not exert a generalized effect on P2X 7 R synthesis or downstream signal transduction. These studies demonstrate that elevated cAMP negatively modulates P2X 7 R expression. J. Leukoc. Biol . 64: 265–273; 1998.