Nuclear factor-κB augments β2-adrenergic receptor expression in human airway epithelial cells

Abstract

Interleukin (IL)-1β increases β2-adrenergic receptor (β2-AR) mRNA and density by protein kinase C (PKC)-dependent mechanisms in human airway epithelial cells. The present study examined the role of several nuclear transcription factors in the PKC-activated upregulation of β2-AR expression. BEAS-2B cells were exposed to the PKC activator phorbol 12-myristate 13-acetate (PMA; 0.1 μM for 2–18 h). PMA had no effect on activator protein (AP)-2 or cAMP response element binding protein DNA binding activity but markedly increased nuclear factor (NF)-κB and AP-1 binding as assessed by electrophoretic gel mobility shift assay. PMA also increased the activity of a β2-AR promoter-luciferase reporter construct in transiently transfected cells. These effects were inhibited by the PKC inhibitors Ro-31-8220 and calphostin C. Furthermore, with increasing Ro-31-8220, β2-AR promoter-reporter activity correlated closely with both NF-κB and AP-1 activities ( r > 0.89 for both). Finally, the selective NF-κB inhibitor MG-132 dose dependently reduced NF-κB binding and β2-AR promoter activity but increased AP-1 binding. We conclude that PKC-induced upregulation of β2-AR expression in human airway epithelial cells appears to be mediated, at least in part, by increases in NF-κB activity.