Regulation of bradykinin receptor gene expression in human lung fibroblasts.

Abstract In WI-38 human fibroblasts, interleukin-1β and tumour necrosis factor-α (TNF-α) increased bradykinin B 1 receptor mRNA, which peaked between 2 and 4 h, remaining elevated for 20 h. Binding of the bradykinin B 1 receptor selective ligand [ 3 H]des-Arg 10 -kallidin, also increased, peaking at 4 h and remaining elevated for 20 h. The B max value for [ 3 H]des-Arg 10 -kallidin rose from 280±102 fmol/mg ( n =3) to 701±147 fmol/mg ( n =3), but the K D value remained unaltered (control, 1.04±0.33 nM ( n =3); interleukin-1β, 0.88±0.41 nM ( n =3)). The interleukin-1β-induced [ 3 H]des-Arg 10 -kallidin binding sites were functional receptors, as bradykinin B 1 receptor agonist-induced responses increased in treated cells. Bradykinin B 2 receptor mRNA and [ 3 H]bradykinin binding were upregulated by interleukin-1β, but not TNF-α. The effect of interleukin-1β on bradykinin B 2 receptors was smaller than for bradykinin B 1 receptors. Cycloheximide prevented interleukin-1β-mediated increases in B 1 and B 2 binding, but not mRNA suggesting that de novo synthesis of a transcriptional activator was unnecessary.