Nuclear factor-kappa B augments beta(2)-adrenergic receptor expression in human airway epithelial cells

Interleukin (IL)-1 beta increases beta (2)-adrenergic receptor (beta (2)-AR ) mRNA and density by protein kinase C (PKC)-dependent mechanisms in human airway epithelial cells. The present study examined the role of several nuc lear transcription factors in the PKC-activated upregulation of beta (2)-AR expression. BEAS-2B cells were exposed to the PKC activator phorbol 12-myr istate 13-acetate (PMA; 0.1 muM for 2-18 h). PMA had no effect on activator protein (AP)-2 or cAMP response element binding protein DNA binding activi ty but markedly increased nuclear factor (NF)-kappaB and AP-1 binding as as sessed by electrophoretic gel mobility shift assay. PMA also increased the activity of a beta (2)-AR promoter-luciferase reporter construct in transie ntly transfected cells. These effects were inhibited by the PKC inhibitors Ro-31-8220 and calphostin C. Furthermore, with increasing Ro-31-8220, beta (2)-AR promoter-reporter activity correlated closely with both NF-kappaB an d AP-1 activities (r > 0.89 for both). Finally, the selective NF-kappaB inh ibitor MG-132 dose dependently reduced NF-kappaB binding and beta (2)-AR pr omoter activity but increased AP-1 binding. We conclude that PKC-induced up regulation of beta (2)-AR expression in human airway epithelial cells appea rs to be mediated, at least in part, by increases in NF-kappaB activity.