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 nuclear transcription factors in the PKC-activated upregulation of beta(2)-AR expression. BEAS-2B cells were exposed to the PKC activator phorbol 12-myristate 13-acetate (PMA; 0.1 microM 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)-kappa B and AP-1 binding as assessed by electrophoretic gel mobility shift assay. PMA also increased the activity of a beta(2)-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, beta(2)-AR promoter-reporter activity correlated closely with both NF-kappa B and AP-1 activities (r > 0.89 for both). Finally, the selective NF-kappa B inhibitor MG-132 dose dependently reduced NF-kappa B binding and beta(2)-AR promoter activity but increased AP-1 binding. We conclude that PKC-induced upregulation of beta(2)-AR expression in human airway epithelial cells appears to be mediated, at least in part, by increases in NF-kappa B activity.
Aksoy
M O
MO
Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, Temple University School of Medicine, Philadelphia, Pennsylvania 19140, USA.
Bin
W
W
Yang
Y
Y
Yun-You
D
D
Kelsen
S G
SG
D002460:Cell Line; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D017930:Genes, Reporter / Q000235:genetics; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D007375:Interleukin-1 / Q000378:metabolism; D007976:Leupeptins / Q000494:pharmacology; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009281:Naphthalenes / Q000494:pharmacology; D011401:Promoter Regions, Genetic; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D018343:Receptors, Adrenergic, beta-2 / Q000235:genetics / Q000378:metabolism*; D020545:Respiratory Mucosa / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000031:analogs & derivatives* / Q000494:pharmacology; D018808:Transcription Factor AP-1 / Q000378:metabolism; D015854:Up-Regulation / Q000502:physiology
D004791:Enzyme Inhibitors; D007211:Indoles; D007375:Interleukin-1; D007976:Leupeptins; D016328:NF-kappa B; D009281:Naphthalenes; D018343:Receptors, Adrenergic, beta-2; D018808:Transcription Factor AP-1; C016658:phorbolol myristate acetate; D011493:Protein Kinase C; C058819:calphostin C; D013755:Tetradecanoylphorbol Acetate; C072553:benzyloxycarbonylleucyl-leucyl-leucine aldehyde; C064758:Ro 31-8220