Selective regulation of β‐adrenergic receptor gene expression by interleukin‐1 in cultured human lung tumor cells

The regulation of β‐ and β‐adrenergic receptors (β AR and β 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 AR and βAR were analyzed by computerized curve fitting of 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 βAR than βAR (β: 1.9 ± 0.3 vs. β: 4.0 ± 0.5 fmol/mg protein, means ± SE), but lost most of their βAR upon reaching confluency (β: 2.7 ± 0.4, β: 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 βAR from 0.8 ± 0.3 to 4.2 ± 0.9 fmol/mg, while the density of βAR and the antagonist affinities of both receptors remained unaltered. The IL‐1α‐induced increase in βAR density in confluent cells was antagonized in a concentration‐dependent manner by a recombinant protein antagonist of type I IL‐1 receptors (IC: 0.2 nM). The IL‐1α‐induced increase in βAR density was preceded by an increase in the steady state level of βAR mRNA, while levels of βAR mRNA remained unchanged. IL‐1α increased the stability as well as the rate of transcription of βAR 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 βAR, and that the mechanism of this effect involves increased formation and stability of the βAR message. © 1992 Wiley‐Liss, Inc. Copyright © 1992 Wiley‐Liss, Inc.