Regulation of bradykinin receptor gene expression in human lung fibroblasts

In WI-38 human fibroblasts, interleukin-1 beta and tumour necrosis factor-a lpha (TNF-alpha) increased bradykinin B-1 receptor mRNA, which peaked betwe en 2 and 4 h, remaining elevated for 20 h. Binding of the bradykinin B-1 re ceptor selective ligand [H-3]des-Arg(10)-kallidin, also increased, peaking at 4 h and remaining elevated for 20 h. The B-max value for [H-3]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-1 beta, 0.88 +/- 0.41 nM (n = 3)). The interleukin-1 beta-i nduced [H-3]des-Arg(10)-kallidin binding sites were functional receptors, a s bradykinin B-1 receptor agonist-induced responses increased in treated ce lls. Bradykinin B-2 receptor mRNA and [H-3]bradykinin binding were upregula ted by interleukin-1 beta, but not TNF-alpha. The effect of interleukin-1 b eta on bradykinin B-2 receptors was smaller than for bradykinin B-1 recepto rs, Cycloheximide prevented interleukin-1 beta-mediated increases in B-1 an d B-2 binding, but not mRNA suggesting that de novo synthesis of a transcri ptional activator was unnecessary. (C) 2000 Elsevier Science B.V. All right s reserved.