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>Selective regulation of β2‐adrenergic receptor gene expression by interleukin‐1 in cultured human lung tumor cells
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Selective regulation of β2‐adrenergic receptor gene expression by interleukin‐1 in cultured human lung tumor cells
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机译：Selective regulation of β2‐adrenergic receptor gene expression by interleukin‐1 in cultured human lung tumor cells
AbstractThe regulation of β1‐ and β2‐adrenergic receptors (β1AR and β2AR) and receptor gene expression by interleukin‐1α (IL‐1α) was studied in cultured A549 human lung adenocarcinoma cells. The density and affinity of β1AR and β2AR were analyzed by computerized curve fitting of125I‐pindolol binding and its displacement by subtype selective antagonists. Steady state levels of receptor mRNAs were quantified by DNA excess solution hybridization assays. A549 cells in preconfluent cultures had fewer β1AR than β2AR (β1: 1.9 ± 0.3 vs. β2: 4.0 ± 0.5 fmol/mg protein, means ± SE), but lost most of their β2AR upon reaching confluency (β1: 2.7 ± 0.4, β2: 0.8 ± 0.3 fmol/mg). Incubation of preconfluent cells for 24 hr with 20 pM of human recombinant IL‐1α did not modify the density of either of the βAR subtypes. Similar incubations of confluent cells increased the density of β2AR from 0.8 ± 0.3 to 4.2 ± 0.9 fmol/mg, while the density of β1AR and the antagonist affinities of both receptors remained unaltered. The IL‐1α‐induced increase in β2AR density in confluent cells was antagonized in a concentration‐dependent manner by a recombinant protein antagonist of type I IL‐1 receptors (IC50: 0.2 nM). The IL‐1α‐induced increase in β2AR density was preceded by an increase in the steady state level of β2AR mRNA, while levels of β1AR mRNA remained unchanged. IL‐1α increased the stability as well as the rate of transcription of β2AR mRNA. These findings demonstrate for the first time that activation of type I IL‐1 receptors in A549 cells leads to a cell density‐dependent, selective upregulation of β2AR, and that the mechanism of this effect involves increased for
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