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Selective regulation of β 2 ‐adrenergic receptor gene expression by interleukin‐1 in cultured human lung tumor cells
Author(s) -
Szentendrei Tibor,
LazarWesley Eliane,
Nakane Tokio,
Virmani Mridulika,
Kunos George
Publication year - 1992
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.1041520306
Subject(s) - receptor , microbiology and biotechnology , recombinant dna , biology , pindolol , gene expression , a549 cell , receptor antagonist , messenger rna , antagonist , medicine , endocrinology , chemistry , in vitro , gene , biochemistry
The regulation of β 1 ‐ and β 2 ‐adrenergic receptors (β 1 AR and β 2 AR) and receptor gene expression by interleukin‐1α (IL‐1α) was studied in cultured A549 human lung adenocarcinoma cells. The density and affinity of β 1 AR and β 2 AR were analyzed by computerized curve fitting of 125 I‐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 β 1 AR than β 2 AR (β 1 : 1.9 ± 0.3 vs. β 2 : 4.0 ± 0.5 fmol/mg protein, means ± SE), but lost most of their β 2 AR upon reaching confluency (β 1 : 2.7 ± 0.4, β 2 : 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 β 2 AR from 0.8 ± 0.3 to 4.2 ± 0.9 fmol/mg, while the density of β 1 AR and the antagonist affinities of both receptors remained unaltered. The IL‐1α‐induced increase in β 2 AR density in confluent cells was antagonized in a concentration‐dependent manner by a recombinant protein antagonist of type I IL‐1 receptors (IC 50 : 0.2 nM). The IL‐1α‐induced increase in β 2 AR density was preceded by an increase in the steady state level of β 2 AR mRNA, while levels of β 1 AR mRNA remained unchanged. IL‐1α increased the stability as well as the rate of transcription of β 2 AR 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 β 2 AR, and that the mechanism of this effect involves increased formation and stability of the β 2 AR message. © 1992 Wiley‐Liss, Inc.